Clinical trial NCT05726851: A Study to Assess the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Pharmacodynamics of E2025 in Healthy Participants
Official title: A First-in-Human, Single Ascending Dose and Pharmacokinetic/Pharmacodynamic Study to Assess the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Pharmacodynamics of Intravenous Infusions of E2025 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: E2025
Healthy Participants
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2023-02-14
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Screening up to Day 113
measure: Number of Participants With Clinically Significant Abnormal Laboratory Values
timeFrame: Screening up to Day 113
measure: Number of Participants With Clinically Significant Abnormal Vital Signs Values
timeFrame: Screening up to Day 113
measure: Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs) Findings
timeFrame: Screening up to Day 113
measure: Number of Participants With Clinically Significant Abnormal Physical Examinations Findings
timeFrame: Screening up to Day 113
measure: Number of Participants With Clinically Significant Abnormal Psychiatric Examination Findings
timeFrame: Screening up to Day 8
Secondary outcomes:
measure: Cmax: Maximum Observed Serum Concentration for E2025
timeFrame: Day 1: 0-24 hours up to Day 113
measure: Tmax: Time to Reach Maximum Observed Serum Concentration (Cmax) for E2025
timeFrame: Day 1: 0-24 hours up to Day 113
measure: AUC(0-t): Area Under the Serum Concentration-time Curve From Time Zero to Last Quantifiable Concentration for E2025
timeFrame: Day 1: 0-24 hours up to Day 113
measure: AUC(0-inf): Area Under the Serum Concentration-time Curve From Time Zero to Infinite for E2025
timeFrame: Day 1: 0-24 hours up to Day 113
measure: AUC(0-24h): Area Under the Serum Concentration-time Curve From Time Zero to 24 hours for E2025
timeFrame: Day 1: 0-24 hours
measure: AUC(0-72h): Area Under the Serum Concentration-time Curve From Time Zero to 72 hours for E2025
timeFrame: Day 1: 0-72 hours
measure: AUC(0-672h): Area Under the Serum Concentration-time Curve From Time Zero to 672 hours for E2025
timeFrame: Day 1: 0-672 hours
measure: t1/2: Terminal Elimination Phase Half-life for E2025
timeFrame: Day 1: 0-24 hours up to Day 113
measure: CL/F: Apparent Total Clearance for E2025
timeFrame: Day 1: 0-24 hours up to Day 113
measure: Vss: Volume of Distribution at Steady State for E2025
timeFrame: Day 1: 0-24 hours up to Day 113
measure: Part A: Cerebrospinal Fluid (CSF) Concentrations for E2025
timeFrame: Pre-dose; Days 8 and 29 post-dose
measure: Part B, CSF Cmax: Maximum Observed CSF Concentration for E2025
timeFrame: Day 1: 0-24 hours up to Day 99
measure: Part B, CSF Tmax: Time to Reach Maximum Observed CSF Concentration (Cmax) for E2025
timeFrame: Day 1: 0-24 hours up to Day 99
measure: Part B, CSF AUC(0-24h): Area Under the CSF Concentration-time Curve From Time Zero to 24 hours for E2025
timeFrame: Day 1: 0-24 hours
measure: Part B: Ratio of Cmax in CSF and Cmax in Serum for E2025
timeFrame: Day 1: 0-24 hours up to Day 99
measure: Part B: Ratio of AUC(0-24h) in CSF and AUC(0-24h) in Serum for E2025
timeFrame: Day 1: 0-24 hours
measure: Serum Concentration of Anti- E2025 Antibodies
timeFrame: Day 1 up to Day 113
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: Worldwide Clinical Trials
state: Texas
Study officials:
References: