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A Study to Assess the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Pharmacodynamics of E2025 in Healthy Participants

Phase 1
Completed
Conditions
Healthy Volunteers
Interventions
Drug: Placebo
Registration Number
NCT05726851
Lead Sponsor
Eisai Inc.
Brief Summary

The primary purpose of the study is to evaluate the safety and tolerability of single intravenous (IV) infusions of E2025 in healthy adult participants.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
32
Inclusion Criteria
  • Non-smoking, male or female age greater than or equal to (>=) 18 years and less than or equal to (<=) 55 years old at the time of informed consent. Females must be of nonchildbearing potential
  • Body weight >=50 kilogram (kg) and a Body Mass Index (BMI) >=18 and less than (<) 30 kilogram per square meter (kg/m^2) at Screening
Exclusion Criteria
  • Females who are breastfeeding or pregnant at Screening or Baseline; Females of childbearing potential.
  • Males who have not had a successful vasectomy (confirmed azoospermia) if their female partners are of childbearing potential and are not willing to use a highly effective contraceptive method throughout the study period or for 203 days after their partner's study drug administration.
  • Clinically significant illness that requires medical treatment within 8 weeks or a clinically significant infection that requires medical treatment within 4 weeks of dosing
  • Evidence of disease that may influence the outcome of the study within 4 weeks before dosing; example, psychiatric disorders and disorders of the gastrointestinal tract, liver, kidney, respiratory system, endocrine system, hematological system, neurological system, or cardiovascular system, or participants who have a congenital abnormality in metabolism
  • Any clinically abnormal symptom or organ impairment found by medical history at Screening, and physical examinations, vital signs, ECG finding, or laboratory test results that require medical treatment at Screening
  • A prolonged QT/QTc interval (QTcF >450 millisecond [ms]). A history of risk factors for torsade de pointes or the use of concomitant medications that prolonged the QT/QTc interval
  • Persistent systolic blood pressure (BP) greater than 130 millimeter of mercury (mmHg) or diastolic BP greater than 85 mmHg at Screening or Baseline; Heart rate less than 50 or more than 100 beats per minute at Screening or Baseline
  • Any lifetime history of suicidal ideation or any lifetime history of suicidal behavior as indicated by the Columbia-suicide Severity Rating Scale (C-SSRS) or equivalent scale or via interview with a psychiatrist
  • Any lifetime history of psychiatric disease (including but not limited to depression or other mood disorders, bipolar disorder, psychotic disorders, including schizophrenia, panic attacks, anxiety disorders); any current psychiatric symptoms as indicated by a standard screening tool.
  • Known history of clinically significant drug allergy; known history of food allergies or presently experiencing significant seasonal or perennial allergy at Screening
  • Any history of hypersensitivity reaction to a foreign protein, with clinical features not limited to nasal or conjunctival symptoms such as in allergic rhinitis
  • Known to be human immunodeficiency virus positive and/or active viral hepatitis (hepatitis B core antibody [HBcAb], hepatitis B viral protein [HBcAg], hepatitis B surface antigen [HBsAg], hepatitis C virus antibody [HCVAb]) as demonstrated by positive serology at Screening
  • History of drug or alcohol dependency or abuse within the 2 years before Screening, or a positive urine drug test or breath alcohol test at Screening or Baseline
  • Currently enrolled in another clinical study or used any investigational drug or device within 28 days (or 5*the half-life, whichever is longer) preceding informed consent
  • Receipt of blood products within 4 weeks, or donation of blood within 8 weeks, or donation of plasma within 1 week of dosing
  • Exposure to any biologic drug within 90 days or at least 5 half-lives (whichever is longer), or within 4 weeks for vaccines, before Screening, with the exception of flu (7 days before dosing) and COVID-19 vaccination (14 days before dosing until after the Follow-up visit).
  • Any contraindication to continuous CSF sampling via indwelling lumbar catheter or via lumbar puncture (LP)
  • Participants identified at risk for hemorrhage.
  • Inadequate venous access that would interfere with study drug administration or obtaining blood samples
  • Participants who contravene the restrictions on concomitant medications, food, beverages, physical activities, and others as defined in the protocol

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Part A, Cohort 3: E2025 Dose 3 or PlaceboE2025Participants will receive E2025 Dose 3 or E2025 matching placebo (normal saline) administered as an IV infusion on Day 1.
Part A, Cohort 1: E2025 Dose 1 or PlaceboE2025Participants will receive E2025 Dose 1 or E2025 matching placebo (normal saline) administered as an IV infusion on Day 1.
Part A, Cohort 1: E2025 Dose 1 or PlaceboPlaceboParticipants will receive E2025 Dose 1 or E2025 matching placebo (normal saline) administered as an IV infusion on Day 1.
Part A, Cohort 2: E2025 Dose 2 or PlaceboE2025Participants will receive E2025 Dose 2 or E2025 matching placebo (normal saline) administered as an IV infusion on Day 1.
Part A, Cohort 2: E2025 Dose 2 or PlaceboPlaceboParticipants will receive E2025 Dose 2 or E2025 matching placebo (normal saline) administered as an IV infusion on Day 1.
Part A, Cohort 3: E2025 Dose 3 or PlaceboPlaceboParticipants will receive E2025 Dose 3 or E2025 matching placebo (normal saline) administered as an IV infusion on Day 1.
Part A, Cohort 4: E2025 Dose 4 or PlaceboE2025Participants will receive E2025 Dose 4 or E2025 matching placebo (normal saline) administered as an IV infusion on Day 1.
Part A, Cohort 4: E2025 Dose 4 or PlaceboPlaceboParticipants will receive E2025 Dose 4 or E2025 matching placebo (normal saline) administered as an IV infusion on Day 1.
Part B, Cohort 6: E2025 Dose 3E2025Participants will receive E2025 Dose 3 administered as an IV infusion on Day 1.
Part B Cohort 7: E2025 Dose 4E2025Participants will receive E2025 Dose 4 administered as an IV infusion on Day 1.
Part B, Cohort 5: E2025 Dose 2E2025Participants will receive E2025 Dose 2 administered as an IV infusion on Day 1.
Primary Outcome Measures
NameTimeMethod
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)Screening up to Day 113
Number of Participants With Clinically Significant Abnormal Laboratory ValuesScreening up to Day 113
Number of Participants With Clinically Significant Abnormal Vital Signs ValuesScreening up to Day 113
Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) FindingsScreening up to Day 113
Number of Participants With Clinically Significant Abnormal Physical Examinations FindingsScreening up to Day 113
Number of Participants With Clinically Significant Abnormal Psychiatric Examination FindingsScreening up to Day 8
Secondary Outcome Measures
NameTimeMethod
Part A: Cerebrospinal Fluid (CSF) Concentrations for E2025Pre-dose; Days 8 and 29 post-dose
Part B, CSF Cmax: Maximum Observed CSF Concentration for E2025Day 1: 0-24 hours up to Day 99
Part B, CSF Tmax: Time to Reach Maximum Observed CSF Concentration (Cmax) for E2025Day 1: 0-24 hours up to Day 99
Part B, CSF AUC(0-24h): Area Under the CSF Concentration-time Curve From Time Zero to 24 hours for E2025Day 1: 0-24 hours
Part B: Ratio of Cmax in CSF and Cmax in Serum for E2025Day 1: 0-24 hours up to Day 99
Part B: Ratio of AUC(0-24h) in CSF and AUC(0-24h) in Serum for E2025Day 1: 0-24 hours
Serum Concentration of Anti- E2025 AntibodiesDay 1 up to Day 113
Cmax: Maximum Observed Serum Concentration for E2025Day 1: 0-24 hours up to Day 113
Tmax: Time to Reach Maximum Observed Serum Concentration (Cmax) for E2025Day 1: 0-24 hours up to Day 113
AUC(0-t): Area Under the Serum Concentration-time Curve From Time Zero to Last Quantifiable Concentration for E2025Day 1: 0-24 hours up to Day 113
AUC(0-inf): Area Under the Serum Concentration-time Curve From Time Zero to Infinite for E2025Day 1: 0-24 hours up to Day 113
AUC(0-24h): Area Under the Serum Concentration-time Curve From Time Zero to 24 hours for E2025Day 1: 0-24 hours
AUC(0-72h): Area Under the Serum Concentration-time Curve From Time Zero to 72 hours for E2025Day 1: 0-72 hours
AUC(0-672h): Area Under the Serum Concentration-time Curve From Time Zero to 672 hours for E2025Day 1: 0-672 hours
t1/2: Terminal Elimination Phase Half-life for E2025Day 1: 0-24 hours up to Day 113
CL/F: Apparent Total Clearance for E2025Day 1: 0-24 hours up to Day 113
Vss: Volume of Distribution at Steady State for E2025Day 1: 0-24 hours up to Day 113

Trial Locations

Locations (1)

Worldwide Clinical Trials

🇺🇸

San Antonio, Texas, United States

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