E2814 for Dominantly Inherited Alzheimer's disease

Inclusion criteria

• {"criterion_text":"-10 to +10 EYO (secondary prevention population): within -10 to +10 years (inclusive) of the estimated age at symptom onset, CDR 0 to 1, inclusive; known eligible mutation carrier or at 50% risk (affected parent or sibling);"}
• {"criterion_text":"-25 to -11 EYO (primary prevention population): within 11 to 25 years younger than their estimated age at symptom onset, CDR 0, known carrier or mutation in their family pedigree; if the at-risk parent is deemed a non-carrier at any point, participants will be withdrawn from study."}
• {"criterion_text":"Willing to complete the main study-related testing, evaluations, and procedures."}

Exclusion criteria

• {"criterion_text":"-Participants will be excluded if they have a major or unstable illness that would prevent trial participation or are unable to complete main study related testing. Exclusions include MRI contraindications, required anticoagulation and pregnancy. Participants who know they are mutation non-carriers are not eligible."}

Primary endpoints

• {"endpoint_text":"-The Primary Outcome is defined in the appendix, and may include biomarker, cognitive, or clinical outcomes. Comparisons will be made between active drug, mutation positive placebos, and control groups, e.g. eligible DIAN-OBS participants.","definition_or_measurement_approach":"Defined in the appendix; may include biomarker, cognitive, or clinical outcomes; comparisons between active drug, mutation-positive placebos, and control groups (e.g. eligible DIAN-OBS participants)."}

Secondary endpoints

• {"endpoint_text":"-Assess safety and tolerability of each study drug in individuals who have mutations causing dominantly inherited Alzheimer's disease.","definition_or_measurement_approach":"Assessment of safety and tolerability of each study drug in mutation carriers (standard safety assessments)."}
• {"endpoint_text":"-Biomarker Endpoints used at interim analysis: Assess target engagement with biomarker endpoints specified for each drug based on mechanism of action. Assess AD biomarkers, including soluble biochemical measures (e.g. amyloid-beta and tau), imaging measures of pathology (e.g. amyloid and tau PET), and AD biomarker changes (e.g. atrophy measured by MRI, hypometabolism by FDG PET, and neurodegeneration measured by Neurofilament light).","definition_or_measurement_approach":"Interim biomarker analyses to assess target engagement: CSF/plasma amyloid and tau species, imaging (amyloid and tau PET), MRI measures (atrophy), FDG PET (hypometabolism), neurofilament light."}
• {"endpoint_text":"-Comparison between each drug and placebo in change from baseline for the following measures:a.Clinical measures obtained at baseline and annual visits will be administered at theDIAN-TU site include:-Clinical Dementia Rating™(CDR)including Clinical Dementia Rating Sum of Boxes™(CDRSB)-Clinician's diagnostic assessment-Geriatric Depression Scale(GDS)-Neuropsychiatric Inventory Questionnaire(NPI-Q)-FAS-MMSE also measured at the26week timepoint between annual visits with the below cognitive battery","definition_or_measurement_approach":"Clinical measures include CDR (including CDR-SB), clinician diagnostic assessment, GDS, NPI-Q, FAS, MMSE; change from baseline comparisons versus placebo."}
• {"endpoint_text":"-b.Cognitive measures to obtained at Baseline and every 26 weeks will be administered at the DIAN-TU site or via homehealth nurse trial-certified cognitive rater include:-DIAN Memory Complaint Questionnaire (MAC-Q)-Buschke and Grober Free and Cued Selective Reminding Test Immediate Recall(FCSRT-IR)-Wechsler Memory Scale-Revised(WMS-R) Logical Memory/Paragraph Memory/Alternate Paragraphs for Logical Memory I&II-VersionsA and Alternate Paragraph for Logical Memory I&II-VersionB-Category Fluency -","definition_or_measurement_approach":"Cognitive battery administered at baseline and every 26 weeks (MAC-Q, FCSRT-IR, WMS-R Logical Memory, category fluency) either at site or via certified home-health cognitive rater."}
• {"endpoint_text":"-b. Cognitive measures to be obtained at Baseline and every 26 weeks (~6 months) in will be administered at the DIAN-TU site or via home health nurse trial-certified cognitive rater include: Weschler Adult Intelligence Scale-Revised (WAIS-R) Digit-Symbol Substitution Test - Trailmaking Test parts A & B - Weschler Memory Scale-Revised (WMS-R) Digit Spatial Span Forward and Backward - Ambulatory Research in Cognition (ARC) smartphone-based cognitive assessments (Grids, Prices, Symbols)","definition_or_measurement_approach":"Additional cognitive assessments at baseline and every ~26 weeks: WAIS-R Digit-Symbol, Trail Making A&B, WMS-R Digit Spatial Span, ARC smartphone-based assessments."}
• {"endpoint_text":"-Imaging measures obtained in randomized drug arms include the following:a.Glucose metabolism PET imaging with FDG-PET b.Amyloid PET imaging with [11C]PiB-PET c.TauPET imaging with[18F]MK-6240 d.Structural brain measures with volumetric MRI e.Functional connectivity MRI(fc-MRI) f.Diffusion Tensor Imaging MRI,including diffusion basis spectrum imaging g.Blood flow measures by Arterial Spin Labeling (ASL)MRI h.Assessment of MRI features such as MCH, WMH, cerebral infarctions and ARIA on MRIsequence","definition_or_measurement_approach":"Imaging endpoints: FDG-PET for glucose metabolism, amyloid PET ([11C]PiB), tau PET ([18F]MK-6240), volumetric MRI, fc-MRI, DTI (including diffusion basis spectrum imaging), ASL, and MRI assessment of MCH, WMH, infarctions, ARIA."}
• {"endpoint_text":"-Fluid biomarker measures that may be included as secondary or exploratory endpoints as specified in the drug-specific appendix and/or SAP, include the following: a. CSF and plasma amyloid species analyses b. CSF and plasma tau species analyses c. CSF and plasma neurofilament light chain analyses d. Additional CSF and blood biomarkers of AD, neurodegeneration, neuroinflammation, or other biomarkers","definition_or_measurement_approach":"Fluid biomarker analyses in CSF and plasma: amyloid species, tau species, neurofilament light, and additional CSF/blood biomarkers as specified per drug appendix/SAP."}
• {"endpoint_text":"-Assess longitudinal change in biomarker, cognitive and clinical measures in individuals who do not have mutations causing DIAD (mutation-negative placebo group). Additional drug-specific endpoints may be listed in each drug-specific appendix.","definition_or_measurement_approach":"Longitudinal comparisons of biomarker, cognitive and clinical measures in mutation-negative placebo/control participants; drug-specific endpoints in appendices."}
• {"endpoint_text":"-For E2814 arm:Symptomatic Population(Cohort 1):To determine whetherE2814 is superior to placebo when is concurrently administered with lecanemab in change from Week24 to Week208 in Clinical Dementia Rating Scale Sum of Boxes(CDR-SB)Asymptomatic Population(Cohort 2):To determine whether E2814 is superior to placebo when is administered alone and then concurrently with lecanemab in change from Week0 to Week104(interim analysis)and Week208(final analysis) in CSF phosphorylated tau(ptau217/tot tau)","definition_or_measurement_approach":"E2814-specific endpoints: symptomatic cohort CDR-SB change Week24 to Week208 when co-administered with lecanemab; asymptomatic cohort CSF p-tau217/total tau change Week0 to Week104 (interim) and Week208 (final)."}

Netherlands

Earliest CTIS Part Ii Submission Date

09-07-2024

Latest Decision Or Authorization Date

22-07-2024

Processing Time Days

13

Number Of Sites

1

Number Of Participants

8

Italy

Earliest CTIS Part Ii Submission Date

09-07-2024

Latest Decision Or Authorization Date

12-08-2024

Processing Time Days

34

Number Of Sites

2

Number Of Participants

3

Spain

Earliest CTIS Part Ii Submission Date

09-07-2024

Latest Decision Or Authorization Date

24-07-2024

Processing Time Days

15

Number Of Sites

1

Number Of Participants

8

Ireland

Earliest CTIS Part Ii Submission Date

09-07-2024

Latest Decision Or Authorization Date

29-07-2024

Processing Time Days

20

Number Of Sites

1

Number Of Participants

1

Germany

Earliest CTIS Part Ii Submission Date

09-07-2024

Latest Decision Or Authorization Date

30-07-2024

Processing Time Days

21

Number Of Sites

2

Number Of Participants

4

Primary sponsor

Full Name

Washington University School Of Medicine

Organisation Type

Educational Institution

Country Of Registered Address

United States

Contract research organisations

Name

IQVIA Limited

Responsibilities

Operational and clinical trial services (multiple sponsor duty codes: 1,10,11,12,2,5,6,7,8,9).

Name

Medpace Imaging Core Lab

Responsibilities

Imaging core lab functions and ECG analysis/review.

Name

Almac Clinical Technologies LLC

Responsibilities

Clinical supply / clinical technology support (sponsor duties code: 3).

Name

Signant Health Global LLC

Responsibilities

eCOA/electronic data capture support (sponsor duties code: 7).

Name

Flywheel Exchange Inc.

Responsibilities

Imaging upload portal and data handling.

Third parties

• {"country":"United States","full_name":"Medpace Imaging Core Lab","duties_or_roles":"ECG analysis/review","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"Sponsor duties code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Medical Research Network Limited","duties_or_roles":"Home healthcare/nurses","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Mayo Clinic Hospital Rochester","duties_or_roles":"Imaging MRI QC","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"University Of Michigan","duties_or_roles":"Imaging PET QC","organisation_type":"Educational Institution"}
• {"country":"Germany","full_name":"Eisai GmbH","duties_or_roles":"IP release","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Signant Health Global LLC","duties_or_roles":"Sponsor duties code: 7 (electronic data capture/eCOA support)","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"Multiple sponsor duties (codes: 1,10,11,12,2,5,6,7,8,9) - operational and clinical trial services","organisation_type":"Pharmaceutical company / CRO"}
• {"country":"United States","full_name":"Sage Bionetworks","duties_or_roles":"Sponsor duties code: 7","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"Sponsor duties code: 3","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Flywheel Exchange Inc.","duties_or_roles":"Imaging upload portal; sponsor duties code: 6","organisation_type":"Laboratory/Research/Testing facility"}