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| ID | Type | Description | Link |
|---|---|---|---|
| 2020-005728-12 | EudraCT Number |
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The primary objective of the study is to assess the safety and tolerability of intravenous (IV) infusions of E2814 in participants with dominantly inherited Alzheimer's disease (DIAD), and to evaluate target engagement (TE) of E2814 on microtubule binding region (MTBR)-tau species in cerebrospinal fluid (CSF) in participants with DIAD.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort A, Phase 1b and 2: E2814 | Experimental | Participants will receive E2814 as an intravenous infusion at set intervals over 12 weeks in Phase 1b and over 96 weeks in Phase 2. |
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| Cohort B: E2814 | Experimental | Participants will receive E2814 as an intravenous infusion at set intervals over 52 weeks. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| E2814 | Drug | E2814 intravenous infusion. |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | A TEAE was defined as adverse event (AE) that started at or after the time of administration of study drug or a worsening of severity from Baseline on or after 1st dose up to last assessment. An AE was any untoward medical occurrence in a participant or clinical investigation participant administered an investigational product. An AE did not necessarily have a causal relationship with the medicinal product. SAE was any untoward medical occurrence that at any dose: resulted in death; was life-threatening (that is, the participant was at immediate risk of death from the AE as it occurred; this did not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug). | From first dose of study drug up to 120 weeks |
| Number of Participants With Markedly Abnormal Laboratory Values | Clinical laboratory tests included hematology, clinical chemistry, and urinalysis assessments. Markedly abnormal value was defined as a post-baseline value with an increase from baseline to a grade of 2 or higher on Common Terminology Criteria for Adverse events (CTCAE) Version 5.0 scale. | From first dose of study drug up to 120 weeks |
| Number of Participants With Clinically Significant Change in Vital Signs Values | Vital sign measurements included systolic and diastolic blood pressure, pulse, respiratory rate, body temperature, height and weight assessment. The clinically significant assessment was based on investigator judgement. | From first dose of study drug up to 120 weeks |
| Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings | The clinically significant assessment was based on investigator judgement. |
| Measure | Description | Time Frame |
|---|---|---|
| Cohort A, Cmax: Maximum Observed Plasma Concentration for E2814 | The concentration of E2814 were measured by validated electrochemiluminescence assay methods and/or by a validated immunoprecipitation/purification followed by liquid chromatography with tandem mass spectrometry methods. | Cohort A, E2814 750 mg: Day 1 pre-dose up to 25 hours post-dose; Cohort A, E2814 1500 mg: Day 85 pre-dose up to 25 hours post-dose |
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Inclusion Criteria:
Exclusion Criteria:
Clinically significant illness that required medical treatment within 8 weeks before the 1st dose or a clinically significant infection that required medical treatment within 4 weeks before 1st dose
Females who are breastfeeding or pregnant at Screening or Baseline
Females of childbearing potential who:
Within 3 months before screening, did not use a highly effective method of contraception
Any neurological condition that may be contributing to cognitive impairment above and beyond that caused by the participant's Alzheimer's disease (AD)
History of transient ischemic attacks, stroke, or seizures within 12 months of Screening
History of clinically important carotid or vertebrobasilar stenosis, plaque, or other prominent risk factor for stroke or cerebral haemorrhage (including atrial fibrillation and anticoagulation). Low dose aspirin (less than or equal to [<=] 325 milligram [mg] daily) is not exclusionary
Any current psychiatric diagnosis or symptoms, (example, hallucinations, major depression, or delusions) that could interfere with study procedures in the participant
Geriatric Depression Scale (GDS) score greater than or equal to 8 at Screening
Contraindications to MRI scanning, including but not limited to pacemaker/cardiac defibrillator, neurostimulators, ferromagnetic metal implants (example, in skull and cardiac devices other than those approved as safe for use in MRI scanners)
Evidence of other clinically significant lesions on brain MRI at Screening that could indicate a dementia diagnosis other than AD
Other significant pathological findings on brain MRI at Screening
Hypersensitivity to E2814 or any of the excipients, or to any monoclonal antibody (mAb) treatment
Any immunological disease which is not adequately controlled, or which requires treatment with immunoglobulins, systemic monoclonal antibodies (or derivatives of monoclonal antibodies), systemic immunosuppressants, or plasmapheresis during the study
With a bleeding disorder of current chronic use of anticoagulants (example, warfarin, dabigatran, rivaroxaban or apixaban) or of clopidogrel is exclusionary. Limited (occasional or isolated) use of anticoagulants/antiplatelet compounds in cases such as surgical procedures
Have thyroid stimulating hormone outside of normal range. Other tests of thyroid function with results outside the normal range should only be exclusionary if they are considered clinically significant by the investigator
Hemoglobin A1c (HgbA1c) greater than (>) 8 percent (%) (retesting is permitted if slightly elevated) or poorly controlled insulin-dependent diabetes (including hypoglycemic episodes). Participants may be rescreened after 3 months to allow optimization of diabetic control
Abnormally low serum vitamin B12 levels for the testing laboratory
History of human immunodeficiency virus (HIV) infection, history of hepatitis B infection within the past year, history of hepatitis C infection which has not been adequately treated, or history of spirochete infection of the central nervous system (example, syphilis, Lyme, or borreliosis)
Any other clinically significant abnormalities in physical examination, vital signs, laboratory tests, or ECG at Screening or Baseline which in the opinion of the investigator require further investigation or treatment or which may interfere with study procedures or safety
Malignant neoplasms within 3 years of Screening (except for basal or squamous cell carcinoma in situ of the skin, or localized prostate cancer in male participant, or localized breast cancer in female participants)
Answers "yes" to Columbia-Suicide Severity Rating Scale (C-SSRS) suicidal ideation Type 4 or 5, or any suicidal behavior assessment within 6 months before Screening, at Screening, or at the Baseline Visit, or has been hospitalized or treated for any suicidal behavior in lifetime
Known or suspected history of drug or alcohol abuse or dependence within 2 years before Screening or a positive urine drug test at Screening
Any other medical conditions (example, cardiac, respiratory, gastrointestinal, renal disease) which are not stably and adequately controlled, or which in the opinion of the investigator could affect the participant's safety or interfere with the study assessments
Concurrent participation in a clinical study involving any anti-amyloid therapies (including any mAb therapies) within 6 months before Screening
Concurrent participation in a clinical study involving any anti-tau therapies
Participated in any other investigational medication or device study in the 3 months or 5 half-lives (whichever is longer) of the medication before Screening
Planned surgery which requires general anesthesia that would take place during the study
Visual or hearing impairment that would prevent the participant from performing psychometric tests accurately
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UC San Diego Altman Clinical and Translational Research Insititute Clinic | La Jolla | California | 92037 | United States | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41964075 | Derived | Andreozzi E, Yagi T, Wildsmith K, Rawal S, Horie K, Boyd P, Takahashi E, Barthelemy NR, Aluri J, Charil A, Reilhac A, Gordon BA, Flores S, Verbel D, Sauter N, Benzinger TLS, McDade E, Mummery C; Dominantly Inherited Alzheimer Network (DIAN); Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU); Zhou J, Bateman RJ, Reyderman L. Etalanetug (E2814) in dominantly inherited Alzheimer's disease: an open-label phase 1b/2 study to assess safety and target engagement in participants with mild to moderate cognitive impairment. Alzheimers Res Ther. 2026 Apr 10;18(1):87. doi: 10.1186/s13195-026-02047-y. |
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Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.
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The study was conducted in two cohorts (Cohort A [Phase 1b and 2] and Cohort B). A total of 11 participants were screened, of which 3 were screen failures and 8 were enrolled to receive study treatment.
Participants took part in the study at 3 investigative sites in the United States and United Kingdom from 28 June 2021 and 24 May 2024.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort A: E2814 | Participants received E2814 intravenous (IV) infusion, every 4 weeks (Q4W) at dose of 750 milligrams (mg) for 12 weeks, followed by 1500 mg for 12 weeks, further followed by 3000 mg for 12 weeks and then 4500 mg for up to 72 weeks. |
| FG001 | Cohort B: E2814 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Dec 1, 2023 | May 23, 2025 |
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| From first dose of study drug up to 120 weeks |
| Cohort A: Change From Baseline in Cerebrospinal Fluid (CSF) Free, CSF Bound and Total Microtubule Binding Region of Tau (MTBR-tau; Starting at Amino Acid 354 and 299) at 12 Weeks | Total MTBR-Tau was the total of bound MTBR-Tau + free MTBR-Tau. CSF samples were collected for the assessment. | Pre-dose at Week 12 |
| Cohort A, Tmax: Time to Reach the Maximum Plasma Concentration for E2814 | The concentration of E2814 was measured by validated electrochemiluminescence assay methods and/or by a validated immunoprecipitation/purification followed by liquid chromatography with tandem mass spectrometry methods. | Cohort A, E2814 750 mg: Day 1 pre-dose up to 25 hours post-dose; Cohort A, E2814 1500 mg: Day 85 pre-dose up to 25 hours post-dose |
| Cohort A, AUC(0-672h): Area Under the Plasma Concentration-time Curve From Zero Time to 672 Hours for E2814 | The concentration of E2814 was measured by validated electrochemiluminescence assay methods and/or by a validated immunoprecipitation/purification followed by liquid chromatography with tandem mass spectrometry methods. | Cohort A, E2814 750 mg: Day 1 pre-dose up to 672 hours post-dose; Cohort A, E2814 1500 mg: Day 85 pre-dose up to 672 hours post-dose |
| Cohort A, Cmax: Maximum Observed Serum Concentration for E2814 | The concentration of E2814 was measured by validated electrochemiluminescence assay methods and/or by a validated immunoprecipitation/purification followed by liquid chromatography with tandem mass spectrometry methods. | Cohort A, E2814 750 mg: Day 1 pre-dose up to 25 hours post-dose; Cohort A, E2814 1500 mg: Day 85 pre-dose up to 25 hours post-dose |
| Cohort A, Tmax: Time to Reach the Maximum Serum Concentration for E2814 | The concentration of E2814 was measured by validated electrochemiluminescence assay methods and/or by a validated immunoprecipitation/purification followed by liquid chromatography with tandem mass spectrometry methods. | Cohort A, E2814 750 mg: Day 1 pre-dose up to 25 hours post-dose; Cohort A, E2814 1500 mg: Day 85 pre-dose up to 25 hours post-dose |
| Cohort A, AUC(0-672h): Area Under the Serum Concentration-time Curve From Zero Time to 672 Hours for E2814 | The concentration of E2814 was measured by validated electrochemiluminescence assay methods and/or by a validated immunoprecipitation/purification followed by liquid chromatography with tandem mass spectrometry methods. | Cohort A, E2814 750 mg: Day 1 pre-dose up to 672 hours post-dose; Cohort A, E2814 1500 mg: Day 85 pre-dose up to 672 hours post-dose |
| Cohort A: CSF Concentrations of E2814 | The concentration of E2814 was measured by validated electrochemiluminescence assay methods and/or by a validated immunoprecipitation/purification followed by liquid chromatography with tandem mass spectrometry methods. | Pre-dose at Days 1, 84, 85, 169, 253, 421, and 757 |
| Number of Participants With Treatment-emergent Positive Serum Anti-E2814 Antibody | Anti-E2814 antibodies were measured by validated electrochemiluminescence assay. | From first dose of study drug up to 120 weeks |
| Number of Participants With Treatment-emergent Positive Plasma Anti-E2814 Antibody | Anti-E2814 antibodies were measured by validated electrochemiluminescence assay. | From first dose of study drug up to 120 weeks |
| Cohort A: Change From Baseline in CSF Concentrations of Total MTBR-tau243 | CSF samples were collected for the assessment. | Baseline, and pre-dose at Days 84, 169, 253, 421, 505, 589, and 757 |
| Cohort A: Change From Baseline in CSF Concentrations of Phosphorylated Tau (P-tau) 181, 205, and 217 | CSF samples were collected for the assessment. | Baseline, and pre-dose at Days 84, 169, 253, 421, 505, 589, and 757 |
| Cohort A: Change From Baseline in Ratio of CSF Concentrations of p-Tau/Non-phosphorylated (np) Tau for 181, 217, and 205 | CSF samples were collected for the assessment. | Baseline, and pre-dose at Days 84, 169, 253, 421, 505, 589, and 757 |
| Cohort A: Change From Baseline in Tau Positron Emission Tomography (PET) Standardized Uptake Value Ratio (SUVR) by Region | Tau-PET imaging uses radiotracers to visualize tau protein deposits in the brain for regional assessment of tau pathology. SUVR is ratio of tracer uptake in each of the cingulate, frontal, medial, occipital, parietal, whole cortical, meta temporal, and temporal cortices relative to tracer uptake in the cerebellum. | Baseline, at Weeks 60 and 108 |
| Indiana University School of Medicine, Health Partners, Adult Neurology Clinic |
| Indianapolis |
| Indiana |
| 46202 |
| United States |
| National Hospital for Neurology and Neurosurgery (NHNN) University College London(UCL) Hospitals NHS Foundation Trust | London | WC1N 3BG | United Kingdom |
Participants received E2814 3000 mg, IV infusion, Q4W for 52 weeks. |
| Cohort A: E2814 750 mg | Participants received E2814 750 mg, IV infusion, Q4W for 12 weeks in Phase 1b of Cohort A. |
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| Cohort A: E2814 1500 mg | Participants received E2814 1500 mg, IV infusion, Q4W for 12 weeks in Phase 2 of Cohort A. |
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| Cohort A: E2814 3000 mg | Participants received E2814 3000 mg, IV infusion, Q4W for 12 weeks in Phase 2 of Cohort A. |
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| Cohort A: E2814 4500 mg | Participants received E2814 4500 mg, IV infusion, Q4W for 72 weeks in Phase 2 of Cohort A. |
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| COMPLETED |
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| NOT COMPLETED |
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The Safety Analysis Set was the group of participants who received at least 1 dose of study drug and had at least 1 post-dose safety assessment.
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort A: E2814 | Participants received E2814 IV infusion, Q4W at dose of 750 mg for 12 weeks, followed by 1500 mg for 12 weeks, further followed by 3000 mg for 12 weeks and then 4500 mg for up to 72 weeks. |
| BG001 | Cohort B: E2814 | Participants received E2814 3000 mg, IV infusion, Q4W for 52 weeks. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||
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| Primary | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | A TEAE was defined as adverse event (AE) that started at or after the time of administration of study drug or a worsening of severity from Baseline on or after 1st dose up to last assessment. An AE was any untoward medical occurrence in a participant or clinical investigation participant administered an investigational product. An AE did not necessarily have a causal relationship with the medicinal product. SAE was any untoward medical occurrence that at any dose: resulted in death; was life-threatening (that is, the participant was at immediate risk of death from the AE as it occurred; this did not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug). | The Safety Analysis Set was the group of participants who received at least 1 dose of study drug and had at least 1 post-dose safety assessment. As pre-specified in statistical analysis plan (SAP), the data of Cohort B was combined with Cohort A for E2814 3000 mg group due to same dosing in both cohorts. | Posted | Count of Participants | Participants | From first dose of study drug up to 120 weeks |
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| Primary | Number of Participants With Markedly Abnormal Laboratory Values | Clinical laboratory tests included hematology, clinical chemistry, and urinalysis assessments. Markedly abnormal value was defined as a post-baseline value with an increase from baseline to a grade of 2 or higher on Common Terminology Criteria for Adverse events (CTCAE) Version 5.0 scale. | The Safety Analysis Set was the group of participants who received at least 1 dose of study drug and had at least 1 post-dose safety assessment. As pre-specified in SAP, the data of Cohort B was combined with Cohort A for E2814 3000 mg group due to same dosing in both cohorts. | Posted | Count of Participants | Participants | From first dose of study drug up to 120 weeks |
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| Primary | Number of Participants With Clinically Significant Change in Vital Signs Values | Vital sign measurements included systolic and diastolic blood pressure, pulse, respiratory rate, body temperature, height and weight assessment. The clinically significant assessment was based on investigator judgement. | The Safety Analysis Set was the group of participants who received at least 1 dose of study drug and had at least 1 post-dose safety assessment. As pre-specified in SAP, the data of Cohort B was combined with Cohort A for E2814 3000 mg group due to same dosing in both cohorts. | Posted | Count of Participants | Participants | From first dose of study drug up to 120 weeks |
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| Primary | Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Findings | The clinically significant assessment was based on investigator judgement. | The Safety Analysis Set was the group of participants who received at least 1 dose of study drug and had at least 1 post-dose safety assessment. As pre-specified in SAP, the data of Cohort B was combined with Cohort A for E2814 3000 mg group due to same dosing in both cohorts. | Posted | Count of Participants | Participants | From first dose of study drug up to 120 weeks |
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| Primary | Cohort A: Change From Baseline in Cerebrospinal Fluid (CSF) Free, CSF Bound and Total Microtubule Binding Region of Tau (MTBR-tau; Starting at Amino Acid 354 and 299) at 12 Weeks | Total MTBR-Tau was the total of bound MTBR-Tau + free MTBR-Tau. CSF samples were collected for the assessment. | The Pharmacodynamic (PD) Analysis Set was the group of participants who received at least 1 dose of study drug and had sufficient PD data to derive at least 1 PD parameter. As planned, this outcome measure was assessed for E2814 750 mg only in Cohort A. | Posted | Mean | Standard Deviation | nanogram per milliliter (ng/mL) | Pre-dose at Week 12 |
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| Secondary | Cohort A, Cmax: Maximum Observed Plasma Concentration for E2814 | The concentration of E2814 were measured by validated electrochemiluminescence assay methods and/or by a validated immunoprecipitation/purification followed by liquid chromatography with tandem mass spectrometry methods. | The Pharmacokinetic (PK) Analysis Set was the group of participants who received at least 1 dose of test drug and had sufficient PK data to derive at least 1 PK parameter. As planned, this PK parameter was assessed for E2814 750 mg and 1500 mg only in Cohort A. | Posted | Geometric Mean | Geometric Coefficient of Variation | microgram per milliliter (mcg/mL) | Cohort A, E2814 750 mg: Day 1 pre-dose up to 25 hours post-dose; Cohort A, E2814 1500 mg: Day 85 pre-dose up to 25 hours post-dose |
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| Secondary | Cohort A, Tmax: Time to Reach the Maximum Plasma Concentration for E2814 | The concentration of E2814 was measured by validated electrochemiluminescence assay methods and/or by a validated immunoprecipitation/purification followed by liquid chromatography with tandem mass spectrometry methods. | The PK Analysis Set was the group of participants who received at least 1 dose of test drug and had sufficient PK data to derive at least 1 PK parameter. As planned, this PK parameter was assessed for E2814 750 mg and 1500 mg only in Cohort A. | Posted | Median | Full Range | hours | Cohort A, E2814 750 mg: Day 1 pre-dose up to 25 hours post-dose; Cohort A, E2814 1500 mg: Day 85 pre-dose up to 25 hours post-dose |
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| Secondary | Cohort A, AUC(0-672h): Area Under the Plasma Concentration-time Curve From Zero Time to 672 Hours for E2814 | The concentration of E2814 was measured by validated electrochemiluminescence assay methods and/or by a validated immunoprecipitation/purification followed by liquid chromatography with tandem mass spectrometry methods. | PK Analysis Set was group of participants who received at least 1 dose of test drug and had sufficient PK data to derive at least 1 PK parameter. As planned, this PK parameter was assessed for E2814 750 mg and 1500 mg only in Cohort A. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure (sampling for first dose of 1500 mg was less intense versus the first dose of 750 mg; thus, no participants were evaluable for 1500 mg group for AUC[0-672h]). | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*microgram per milliliter (h*mcg/mL) | Cohort A, E2814 750 mg: Day 1 pre-dose up to 672 hours post-dose; Cohort A, E2814 1500 mg: Day 85 pre-dose up to 672 hours post-dose |
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| Secondary | Cohort A, Cmax: Maximum Observed Serum Concentration for E2814 | The concentration of E2814 was measured by validated electrochemiluminescence assay methods and/or by a validated immunoprecipitation/purification followed by liquid chromatography with tandem mass spectrometry methods. | The PK Analysis Set was the group of participants who received at least 1 dose of test drug and had sufficient PK data to derive at least 1 PK parameter. As planned, this PK parameter was assessed for E2814 750 mg and 1500 mg only in Cohort A. | Posted | Geometric Mean | Geometric Coefficient of Variation | mcg/mL | Cohort A, E2814 750 mg: Day 1 pre-dose up to 25 hours post-dose; Cohort A, E2814 1500 mg: Day 85 pre-dose up to 25 hours post-dose |
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| Secondary | Cohort A, Tmax: Time to Reach the Maximum Serum Concentration for E2814 | The concentration of E2814 was measured by validated electrochemiluminescence assay methods and/or by a validated immunoprecipitation/purification followed by liquid chromatography with tandem mass spectrometry methods. | The PK Analysis Set was the group of participants who received at least 1 dose of test drug and had sufficient PK data to derive at least 1 PK parameter. As planned, this PK parameter was assessed for E2814 750 mg and 1500 mg only in Cohort A. | Posted | Median | Full Range | hours | Cohort A, E2814 750 mg: Day 1 pre-dose up to 25 hours post-dose; Cohort A, E2814 1500 mg: Day 85 pre-dose up to 25 hours post-dose |
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| Secondary | Cohort A, AUC(0-672h): Area Under the Serum Concentration-time Curve From Zero Time to 672 Hours for E2814 | The concentration of E2814 was measured by validated electrochemiluminescence assay methods and/or by a validated immunoprecipitation/purification followed by liquid chromatography with tandem mass spectrometry methods. | PK Analysis Set was group of participants who received at least 1 dose of test drug and had sufficient PK data to derive at least 1 PK parameter. As planned, this PK parameter was assessed for E2814 750 mg and 1500 mg only in Cohort A. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure (sampling for first dose of 1500 mg was less intense versus the first dose of 750 mg; thus, no participants were evaluable for 1500 mg group for AUC[0-672h]). | Posted | Geometric Mean | Geometric Coefficient of Variation | h*mcg/mL | Cohort A, E2814 750 mg: Day 1 pre-dose up to 672 hours post-dose; Cohort A, E2814 1500 mg: Day 85 pre-dose up to 672 hours post-dose |
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| Secondary | Cohort A: CSF Concentrations of E2814 | The concentration of E2814 was measured by validated electrochemiluminescence assay methods and/or by a validated immunoprecipitation/purification followed by liquid chromatography with tandem mass spectrometry methods. | The PK Analysis Set was the group of participants who received at least 1 dose of test drug and had sufficient PK data to derive at least 1 PK parameter. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and "Number Analyzed" signifies participants evaluable at given time points for specified dosing group. | Posted | Mean | Standard Deviation | ng/mL | Pre-dose at Days 1, 84, 85, 169, 253, 421, and 757 |
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| Secondary | Number of Participants With Treatment-emergent Positive Serum Anti-E2814 Antibody | Anti-E2814 antibodies were measured by validated electrochemiluminescence assay. | The Safety Analysis Set was the group of participants who received at least 1 dose of study drug and had at least 1 post-dose safety assessment. As pre-specified in SAP, the data of Cohort B was combined with Cohort A for E2814 3000 mg group due to same dosing in both cohorts. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. | Posted | Count of Participants | Participants | From first dose of study drug up to 120 weeks |
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| Secondary | Number of Participants With Treatment-emergent Positive Plasma Anti-E2814 Antibody | Anti-E2814 antibodies were measured by validated electrochemiluminescence assay. | The Safety Analysis Set was the group of participants who received at least 1 dose of study drug and had at least 1 post-dose safety assessment. As pre-specified in SAP, the data of Cohort B was combined with Cohort A for E2814 3000 mg group due to same dosing in both cohorts. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. | Posted | Count of Participants | Participants | From first dose of study drug up to 120 weeks |
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| Secondary | Cohort A: Change From Baseline in CSF Concentrations of Total MTBR-tau243 | CSF samples were collected for the assessment. | The PD Analysis Set was the group of participants who received at least 1 dose of study drug and had sufficient PD data to derive at least 1 PD parameter. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and "Number Analyzed" signifies participants evaluable at given time points for specified dosing group. | Posted | Mean | Standard Deviation | picogram per milliliter (pg/mL) | Baseline, and pre-dose at Days 84, 169, 253, 421, 505, 589, and 757 |
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| Secondary | Cohort A: Change From Baseline in CSF Concentrations of Phosphorylated Tau (P-tau) 181, 205, and 217 | CSF samples were collected for the assessment. | The PD Analysis Set was the group of participants who received at least 1 dose of study drug and had sufficient PD data to derive at least 1 PD parameter. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and "Number Analyzed" signifies participants evaluable at given time points for specified dosing group. | Posted | Mean | Standard Deviation | pg/mL | Baseline, and pre-dose at Days 84, 169, 253, 421, 505, 589, and 757 |
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| Secondary | Cohort A: Change From Baseline in Ratio of CSF Concentrations of p-Tau/Non-phosphorylated (np) Tau for 181, 217, and 205 | CSF samples were collected for the assessment. | The PD Analysis Set was the group of participants who received at least 1 dose of study drug and had sufficient PD data to derive at least 1 PD parameter. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and "Number Analyzed" signifies participants evaluable at given time points for specified dosing group. | Posted | Mean | Standard Deviation | ratio | Baseline, and pre-dose at Days 84, 169, 253, 421, 505, 589, and 757 |
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| Secondary | Cohort A: Change From Baseline in Tau Positron Emission Tomography (PET) Standardized Uptake Value Ratio (SUVR) by Region | Tau-PET imaging uses radiotracers to visualize tau protein deposits in the brain for regional assessment of tau pathology. SUVR is ratio of tracer uptake in each of the cingulate, frontal, medial, occipital, parietal, whole cortical, meta temporal, and temporal cortices relative to tracer uptake in the cerebellum. | The PD Analysis Set was the group of participants who received at least 1 dose of study drug and had sufficient PD data to derive at least 1 PD parameter. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. As planned, this outcome measure was assessed for 4500 mg only in Cohort A. | Posted | Mean | Standard Deviation | SUVR | Baseline, at Weeks 60 and 108 |
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From first dose of study drug up to 120 weeks
As pre-specified in SAP, the data of Cohort B was combined with Cohort A for E2814 3000 mg group due to same dosing in both cohorts.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort A: E2814 750 mg | Participants received E2814 750 mg, IV infusion, Q4W for 12 weeks. | 0 | 7 | 0 | 7 | 4 | 7 |
| EG001 | Cohort A: E2814 1500 mg | Participants received E2814 1500 mg, IV infusion, Q4W for 12 weeks. | 0 | 7 | 0 | 7 | 1 | 7 |
| EG002 | Cohort A+B: E2814 3000 mg | Participants received E2814 3000 mg, IV infusion, Q4W for 12 weeks in Cohort A and for 52 weeks in Cohort B. | 0 | 8 | 2 | 8 | 7 | 8 |
| EG003 | Cohort A: E2814 4500 mg | Participants received E2814 4500 mg, IV infusion, Q4W for up to 72 weeks. | 0 | 4 | 1 | 4 | 4 | 4 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lower respiratory tract infection | Infections and infestations | MedDRA Version 27.0 | Systematic Assessment |
| |
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA Version 27.0 | Systematic Assessment |
| |
| Cerebral venous sinus thrombosis | Nervous system disorders | MedDRA Version 27.0 | Systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA Version 27.0 | Systematic Assessment |
| |
| Vaginal haemorrhage | Reproductive system and breast disorders | MedDRA Version 27.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bundle branch block left | Cardiac disorders | MedDRA Version 27.0 | Systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA Version 27.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA Version 27.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA Version 27.0 | Systematic Assessment |
| |
| Gait disturbance | General disorders | MedDRA Version 27.0 | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA Version 27.0 | Systematic Assessment |
| |
| Peripheral swelling | General disorders | MedDRA Version 27.0 | Systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA Version 27.0 | Systematic Assessment |
| |
| Fungal infection | Infections and infestations | MedDRA Version 27.0 | Systematic Assessment |
| |
| Fungal skin infection | Infections and infestations | MedDRA Version 27.0 | Systematic Assessment |
| |
| Genital herpes | Infections and infestations | MedDRA Version 27.0 | Systematic Assessment |
| |
| Hordeolum | Infections and infestations | MedDRA Version 27.0 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA Version 27.0 | Systematic Assessment |
| |
| Otitis media | Infections and infestations | MedDRA Version 27.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA Version 27.0 | Systematic Assessment |
| |
| Clavicle fracture | Injury, poisoning and procedural complications | MedDRA Version 27.0 | Systematic Assessment |
| |
| Eye injury | Injury, poisoning and procedural complications | MedDRA Version 27.0 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA Version 27.0 | Systematic Assessment |
| |
| Rib fracture | Injury, poisoning and procedural complications | MedDRA Version 27.0 | Systematic Assessment |
| |
| Skin laceration | Injury, poisoning and procedural complications | MedDRA Version 27.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA Version 27.0 | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA Version 27.0 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA Version 27.0 | Systematic Assessment |
| |
| Chronic lymphocytic leukaemia recurrent | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA Version 27.0 | Systematic Assessment |
| |
| Skin papilloma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA Version 27.0 | Systematic Assessment |
| |
| Aphasia | Nervous system disorders | MedDRA Version 27.0 | Systematic Assessment |
| |
| Bradykinesia | Nervous system disorders | MedDRA Version 27.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA Version 27.0 | Systematic Assessment |
| |
| Hemiapraxia | Nervous system disorders | MedDRA Version 27.0 | Systematic Assessment |
| |
| Migraine | Nervous system disorders | MedDRA Version 27.0 | Systematic Assessment |
| |
| Myoclonus | Nervous system disorders | MedDRA Version 27.0 | Systematic Assessment |
| |
| Tension headache | Nervous system disorders | MedDRA Version 27.0 | Systematic Assessment |
| |
| Agitation | Psychiatric disorders | MedDRA Version 27.0 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA Version 27.0 | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA Version 27.0 | Systematic Assessment |
| |
| Delusion | Psychiatric disorders | MedDRA Version 27.0 | Systematic Assessment |
| |
| Hallucination | Psychiatric disorders | MedDRA Version 27.0 | Systematic Assessment |
| |
| Hallucination, visual | Psychiatric disorders | MedDRA Version 27.0 | Systematic Assessment |
| |
| Hypertonic bladder | Renal and urinary disorders | MedDRA Version 27.0 | Systematic Assessment |
| |
| Micturition urgency | Renal and urinary disorders | MedDRA Version 27.0 | Systematic Assessment |
| |
| Chronic pigmented purpura | Skin and subcutaneous tissue disorders | MedDRA Version 27.0 | Systematic Assessment |
| |
| Cold sweat | Skin and subcutaneous tissue disorders | MedDRA Version 27.0 | Systematic Assessment |
| |
| Vasculitis | Vascular disorders | MedDRA Version 27.0 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA Version 27.0 | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Eisai Medical Information | Eisai Inc. | +1-888-274-2378 | esi_medinfo@eisai.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 23, 2024 | May 23, 2025 | SAP_001.pdf |
| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| D008224 | Lymphoma, Follicular |
| D002493 | Central Nervous System Diseases |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D009422 | Nervous System Diseases |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D008228 | Lymphoma, Non-Hodgkin |
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
Not provided
Not provided
| >=65 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Serious TEAEs |
|
| Cohort A: E2814 4500 mg |
Participants received E2814 4500 mg, IV infusion, Q4W for up to 72 weeks. |
|
|
Participants received E2814 4500 mg, IV infusion, Q4W for up to 72 weeks. |
|
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|
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| Units | Counts |
|---|---|
| Participants |
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| Units | Counts |
|---|
| Participants |
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Participants received E2814 4500 mg, IV infusion, Q4W for up to 72 weeks. |
|
|
Participants received E2814 4500 mg, IV infusion, Q4W for up to 72 weeks. |
|
|
Participants received E2814 4500 mg, IV infusion, Q4W for up to 72 weeks. |
|
|
Participants received E2814 4500 mg, IV infusion, Q4W for up to 72 weeks.
|
|
Participants received E2814 4500 mg, IV infusion, Q4W for up to 72 weeks.
|
|
Participants received E2814 4500 mg, IV infusion, Q4W for up to 72 weeks.
|
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