A Study to Assess Safety, Tolerability, Pharmacokinetics (PK), Immunogenicity, and Pharmacodynamics (PD) of Intravenous Infusions of E2814 in Healthy Participants

• ClinicalTrials.gov Identifier: NCT04231513
• Recruitment Status: Recruiting
• First Posted: January 18, 2020
• Last Update Posted: April 4, 2022
• Sponsor: Eisai Inc.
• Information provided by (Responsible Party): Eisai Inc.

Study Description

Brief Summary:

The primary objective of this study is to evaluate the safety and tolerability of single and multiple intravenous infusions of E2814 in healthy adult participants.

Condition or disease	Intervention/treatment	Phase
Healthy Volunteers	Drug: E2814; Drug: E2814-matched placebo	Phase 1

Detailed Description:

The study is comprised of two components: a single ascending dose (SAD) component and a multiple ascending dose (MAD) component. The SAD component consists of 5 sequential cohorts and in each cohort, 8 healthy participants are randomized (3:1) to receive a single dose of E2814 or E2814-matched placebo. The MAD component of the study consists of 4 sequential cohorts and in each cohort, 8 healthy participants are randomized (3:1) to receive E2814 or E2814-matched placebo every 4 weeks (Q4W) on 3 occasions.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 72 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Other
• Official Title: A Randomized, Double-Blind, Placebo-Controlled, Combined Single Ascending Dose and Multiple Ascending Dose Study to Assess Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Pharmacodynamics of Intravenous Infusions of E2814 in Healthy Subjects
• Actual Study Start Date: December 16, 2019
• Estimated Primary Completion Date: January 5, 2023
• Estimated Study Completion Date: January 5, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: SAD, Cohort 1: E2814 or E2814-matched Placebo; Participants will receive either E2814 or E2814-matched placebo as an intravenous infusion, once, on Day 1.	Drug: E2814; E2814, intravenous infusion.; Drug: E2814-matched placebo; E2814-matched placebo, intravenous infusion.
Experimental: SAD, Cohort 2: E2814 or E2814-matched Placebo; Participants will receive either E2814 or E2814-matched placebo as an intravenous infusion, once, on Day 1.	Drug: E2814; E2814, intravenous infusion.; Drug: E2814-matched placebo; E2814-matched placebo, intravenous infusion.
Experimental: SAD, Cohort 3: E2814 or E2814-matched Placebo; Participants will receive either E2814 or E2814-matched placebo as an intravenous infusion, once, on Day 1.	Drug: E2814; E2814, intravenous infusion.; Drug: E2814-matched placebo; E2814-matched placebo, intravenous infusion.
Experimental: SAD, Cohort 4: E2814 or E2814-matched Placebo; Participants will receive either E2814 or E2814-matched placebo as an intravenous infusion, once, on Day 1.	Drug: E2814; E2814, intravenous infusion.; Drug: E2814-matched placebo; E2814-matched placebo, intravenous infusion.
Experimental: SAD, Cohort 5: E2814 or E2814-matched Placebo; Participants will receive either E2814 or E2814-matched placebo as an intravenous infusion, once, on Day 1.	Drug: E2814; E2814, intravenous infusion.; Drug: E2814-matched placebo; E2814-matched placebo, intravenous infusion.
Experimental: MAD, Cohort 1: E2814 or E2814-matched Placebo; Participants will receive E2814 or E2814-matched placebo as an intravenous infusion Q4W on 3 occasions up to Day 57 of the Treatment Period.	Drug: E2814; E2814, intravenous infusion.; Drug: E2814-matched placebo; E2814-matched placebo, intravenous infusion.
Experimental: MAD, Cohort 2: E2814 or E2814-matched Placebo; Participants will receive E2814 or E2814-matched placebo as an intravenous infusion Q4W on 3 occasions up to Day 57 of the Treatment Period.	Drug: E2814; E2814, intravenous infusion.; Drug: E2814-matched placebo; E2814-matched placebo, intravenous infusion.
Experimental: MAD, Cohort 3: E2814 or E2814-matched Placebo; Participants will receive E2814 or E2814-matched placebo as an intravenous infusion Q4W on 3 occasions up to Day 57 of the Treatment Period.	Drug: E2814; E2814, intravenous infusion.; Drug: E2814-matched placebo; E2814-matched placebo, intravenous infusion.
Experimental: MAD, Cohort 4: E2814 or E2814-matched Placebo; Participants will receive E2814 or E2814-matched placebo as an intravenous infusion Q4W on 3 occasions up to Day 57 of the Treatment Period.	Drug: E2814; E2814, intravenous infusion.; Drug: E2814-matched placebo; E2814-matched placebo, intravenous infusion.

Outcome Measures

Primary Outcome Measures :

1. SAD, Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to 113 days ]
2. SAD, Number of Participants With Clinically Significant Laboratory Values [ Time Frame: Up to 113 days ]
3. SAD, Number of Participants With Clinically Significant Vital Signs Values [ Time Frame: Up to 113 days ]
4. SAD, Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings [ Time Frame: Up to 113 days ]
5. MAD, Number of Participants With TEAEs and SAEs [ Time Frame: Up to 169 days ]
6. MAD, Number of Participants With Clinically Significant Laboratory Values [ Time Frame: Up to 169 days ]
7. MAD, Number of Participants With Clinically Significant Vital Signs Values [ Time Frame: Up to 169 days ]
8. MAD, Number of Participants With Clinically Significant ECG Findings [ Time Frame: Up to 169 days ]

Secondary Outcome Measures :

1. SAD, Cmax Serum: Maximum Observed Concentration for E2814 [ Time Frame: Pre-dose (Day 1) and up to Day 113 Post Dose ]
2. SAD, Tmax Serum: Time to Reach the Maximum Observed Concentration (Cmax) for E2814 [ Time Frame: Pre-dose (Day 1) and up to Day 113 Post Dose ]
3. SAD, AUC (0-24h) Serum: Area Under the Concentration-time Curve From Time Zero to 24 Hour for E2814 [ Time Frame: Pre-dose (Day 1) and up to 24 hours Post Dose ]
4. SAD, AUC (0-72h) Serum: Area Under the Concentration-time Curve From Time Zero to 72 Hour for E2814 [ Time Frame: Pre-dose (Day 1) and up to 72 hours Post Dose ]
5. SAD, AUC (0-inf) Serum: Area Under the Concentration-time Curve from Time 0 to Infinity for E2814 [ Time Frame: Pre-dose (Day 1) and up to Day 113 Post Dose ]
6. SAD, t½ Serum: Terminal Elimination Phase Half-life for E2814 [ Time Frame: Pre-dose (Day 1) and up to Day 113 Post Dose ]
7. SAD, CL Serum: Clearance for E2814 [ Time Frame: Pre-dose (Day 1) and up to Day 113 Post Dose ]
8. SAD, Vz Serum: Volume of Distribution for E2814 [ Time Frame: Pre-dose (Day 1) and up to Day 113 Post Dose ]
9. SAD, Serum anti-E2814 Antibody Concentration [ Time Frame: Pre-dose (Day 1) and up to Day 113 Post Dose ]
10. SAD, Cmax CSF: Maximum Observed Concentration for E2814 [ Time Frame: Pre-dose (Day 1) and up to Day 29 Post Dose ]
11. SAD, Tmax CSF: Time to Reach the Maximum Observed Concentration (Cmax) for E2814 [ Time Frame: Pre-dose (Day 1) and up to Day 29 Post Dose ]
12. SAD, AUC (0-24h) CSF: Area Under the Concentration-time Curve From Time Zero to 24 Hour for E2814 [ Time Frame: Pre-dose (Day 1) and up to 24 hours Post Dose ]
13. SAD, Cmax Plasma: Maximum Observed Concentration for E2814 [ Time Frame: Pre-dose (Day 1) and up to Day 113 Post Dose ]
14. SAD, Tmax Plasma: Time to Reach the Maximum Observed Concentration (Cmax) for E2814 [ Time Frame: Pre-dose (Day 1) and up to Day 113 Post Dose ]
15. SAD, AUC (0-24h) Plasma: Area Under the Concentration-time Curve From Time Zero to 24 Hour for E2814 [ Time Frame: Pre-dose (Day 1) and up to 24 hours Post Dose ]
16. SAD, AUC (0-72h) Plasma: Area Under the Concentration-time Curve From Time Zero to 72 Hour for E2814 [ Time Frame: Pre-dose (Day 1) and up to 72 hours Post Dose ]
17. SAD, AUC (0-inf) Plasma: Area Under the Concentration-time Curve from Time 0 to Infinity for E2814 [ Time Frame: Pre-dose (Day 1) and up to Day 113 Post Dose ]
18. SAD, t½ Plasma: Terminal Elimination Phase Half-life for E2814 [ Time Frame: Pre-dose (Day 1) and up to Day 113 Post Dose ]
19. SAD, CL Plasma: Clearance for E2814 [ Time Frame: Pre-dose (Day 1) and up to Day 113 Post Dose ]
20. SAD, Vz Plasma: Volume of Distribution for E2814 [ Time Frame: Pre-dose (Day 1) and up to Day 113 Post Dose ]
21. SAD, Plasma anti-E2814 Antibody Concentration [ Time Frame: Pre-dose (Day 1) and up to Day 113 Post Dose ]
22. MAD, Cmax Serum: Maximum Observed Concentration for E2814 [ Time Frame: Pre-dose (Day 1) and up to Day 169 Post Dose ]
23. MAD, Tmax Serum: Time to Reach the Maximum Observed Concentration (Cmax) for E2814 [ Time Frame: Pre-dose (Day 1) and up to Day 169 Post Dose ]
24. MAD, AUC (0-24h) Serum: Area Under the Concentration-time Curve From Time Zero to 24 Hour for E2814 [ Time Frame: Pre-dose (Day 1) and up to 24 hours Post Dose ]
25. MAD, AUC (0-72h) Serum: Area Under the Concentration-time Curve From Time Zero to 72 Hour for E2814 [ Time Frame: Pre-dose (Day 1) and up to 72 hours Post Dose ]
26. MAD, AUC (0-tau) Serum: Area Under the Concentration-time Curve From Zero Time to the end of the Dosing Interval for E2814 [ Time Frame: Pre-dose (Day 1) and up to Day 169 Post Dose ]
27. MAD, t½ Serum: Terminal Elimination Half-life for E2814 [ Time Frame: Pre-dose (Day 1) and up to Day 169 Post Dose ]
28. MAD, CL Serum: Clearance for E2814 [ Time Frame: Pre-dose (Day 1) and up to Day 169 Post Dose ]
29. MAD, Vz Serum: Volume of Distribution for E2814 [ Time Frame: Pre-dose (Day 1) and up to Day 169 Post Dose ]
30. MAD, Rac(Cmax) Serum: Ratio of Accumulation for Cmax for E2814 [ Time Frame: Pre-dose (Day 1) and up to Day 169 Post Dose ]
31. MAD, Rac(AUC) Serum: Ratio of Accumulation for AUC for E2814 [ Time Frame: Pre-dose (Day 1) and up to Day 169 Post Dose ]
32. MAD, Serum anti-E2814 Antibody Concentration [ Time Frame: Pre-dose (Day 1) and up to Day 169 Post Dose ]
33. MAD, CSF Concentration for E2814 [ Time Frame: Pre-dose (Day 1) and up to Day 85 Post Dose ]
34. MAD, Cmax Plasma: Maximum Observed Concentration for E2814 [ Time Frame: Pre-dose (Day 1) and up to Day 169 Post Dose ]
35. MAD, Tmax Plasma: Time to Reach the Maximum Observed Concentration (Cmax) for E2814 [ Time Frame: Pre-dose (Day 1) and up to Day 169 Post Dose ]
36. MAD, AUC (0-24h) Plasma: Area Under the Concentration-time Curve From Time Zero to 24 Hour for E2814 [ Time Frame: Pre-dose (Day 1) and up to 24 hours Post Dose ]
37. MAD, AUC (0-72h) Plasma: Area Under the Concentration-time Curve From Time Zero to 72 Hour for E2814 [ Time Frame: Pre-dose (Day 1) and up to 72 hours Post Dose ]
38. MAD, AUC (0-tau) Plasma: Area Under the Concentration-time Curve From Zero Time to the end of the Dosing Interval for E2814 [ Time Frame: Pre-dose (Day 1) and up to Day 169 Post Dose ]
39. MAD, t½ Plasma: Terminal Elimination Half-life for E2814 [ Time Frame: Pre-dose (Day 1) and up to Day 169 Post Dose ]
40. MAD, CL Plasma: Clearance for E2814 [ Time Frame: Pre-dose (Day 1) and up to Day 169 Post Dose ]
41. MAD, Vz Plasma: Volume of Distribution for E2814 [ Time Frame: Pre-dose (Day 1) and up to Day 169 Post Dose ]
42. MAD, Rac(Cmax) Plasma: Ratio of Accumulation for Cmax for E2814 [ Time Frame: Pre-dose (Day 1) and up to Day 169 Post Dose ]
43. MAD, Rac(AUC) Plasma: Ratio of Accumulation for AUC for E2814 [ Time Frame: Pre-dose (Day 1) and up to Day 169 Post Dose ]
44. MAD, Plasma anti-E2814 Antibody Concentration [ Time Frame: Pre-dose (Day 1) and up to Day 169 Post Dose ]

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. Nonsmoking, healthy participants.

Japanese participants must satisfy the following requirements:

1. Must have been born in Japan to Japanese parents and Japanese grandparents
2. Must have lived no more than 5 years outside of Japan
3. Must not have changed their life style or habits, including diet, while living outside of Japan

Exclusion Criteria:

1. Clinically significant illness that requires medical treatment within 8 weeks or a clinically significant infection that requires medical treatment within 4 weeks of dosing
2. Females who are breastfeeding or pregnant at Screening or Baseline

3. Females of childbearing potential who within 28 days before study entry, did not use a highly effective method of contraception, which includes any of the following:

   1. total abstinence (if it is their preferred and usual lifestyle)
   2. an intrauterine device or intrauterine hormone-releasing system
   3. a contraceptive implant
   4. an oral contraceptive (Participants must be on a stable dose of the same oral contraceptive product for at least 28 days before dosing and throughout the study and for 16 weeks after study drug discontinuation)
   5. have a vasectomized partner with confirmed azoospermia Do not agree to use a highly effective method of contraception (as described above) throughout the entire study period and for 16 weeks after study drug discontinuation NOTE: All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (that is, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing).
4. Males who have not had a successful vasectomy (confirmed azoospermia) or they and their female partners do not meet the criteria above (that is, not of childbearing potential or practicing highly effective contraception throughout the study period and for 5 times the half-life of the study drug plus 90 days after study drug discontinuation). If the female partner is pregnant, then males who do not agree to use latex, or synthetic condoms throughout the study period and for 90 days after study drug discontinuation. No sperm donation is allowed during the study period and for 5 times the half-life of the study drug plus 90 days after study drug discontinuation
5. 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
6. Any clinically abnormal symptom or organ impairment found by medical history, physical examinations, vital signs, ECG finding, or laboratory test results that requires medical treatment at Screening or Baseline
7. A prolonged QT (that is, corrected QT interval [QTc] Fridericia interval greater than [>] 450 milliseconds) demonstrated on ECG at Screening or Baseline. A history of risk factors for torsade de pointes (example, heart failure, hypokalemia, family history of long QT Syndrome)
8. Persistent systolic blood pressure (SBP) >130 millimeters of mercury (mmHg) or diastolic blood pressure (DBP) >85 mmHg at Screening or Baseline. One repeat measurement will be allowed
9. Heart rate less than 45 or more than 100 beats per minute at Screening or Baseline
10. Known history of clinically significant drug allergy at Screening or Baseline
11. Known history of food allergies or presently experiencing significant seasonal or perennial allergy at Screening or Baseline
12. Any history of hypersensitivity reaction to a foreign protein, with clinical features of Grades 2 to 4 as described in National Cancer Institute-Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, immunoglobulin A (IgA) deficiency, or significant autoimmune disease or disorder. Participants with hypersensitivity reactions to foreign protein with clinical features limited to nasal or conjunctival symptoms such as in allergic rhinitis do not need to be excluded
13. Known to be human immunodeficiency virus (HIV) positive at Screening
14. Active or chronic (including asymptomatic) viral hepatitis (A, B or C) as demonstrated by positive serology at Screening. For hepatitis B serology, this refers to positive for hepatitis B core antibody (HBcAb, Immunoglobulin M [IgM] type) or hepatitis B surface or core antigens (HBsAg, HBcAg). For hepatitis C serology, a positive result for screening serological testing must be confirmed by qualitative hepatitis C virus ribonucleic acid (RNA)
15. History of drug or alcohol dependency or abuse within the 2 years before Screening, or those who have a positive urine drug test or breath (or urine) alcohol test at Screening or Baseline
16. Intake of over-the-counter medications within 2 weeks before dosing
17. Currently enrolled in another clinical study or used any investigational drug or device within 30 days (or 5 half-lives, whichever is longer) preceding informed consent
18. 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 influenza and COVID-19 vaccinations that are allowed up to 7 days before dosing
19. Engagement in strenuous exercise within 2 weeks before check-in (example, marathon runners, weight lifters, etc.)
20. Any contraindication to continuous cerebrospinal fluid (CSF) sampling via indwelling lumbar catheter or via lumbar puncture (LP)
21. Any history of or current blood clotting or bleeding disorder that is not under adequate control, including a platelet count less than (<) 50,000, international normalized ratio (INR) >1.3, or partial thromboplastin time (PTT) >upper limit of normal (ULN), or fibrinogen <1.8 gram per liter (g/L) or >4.3 g/L at Screening or Baseline. Participants receiving anticoagulation therapy or identified at risk for hemorrhage
22. Any lifetime suicidal behavior or psychiatric disease. Whenever possible, medical records should be reviewed to confirm absence of history of psychiatric disease or use of medications to treat psychiatric disease
23. Any current or prior history of suicidal behavior or psychiatric disease identified by the psychiatrist at the Screening Visit

Contacts and Locations

Contacts

Contact: Eisai Medical Information; +1-888-274-2378; esi_medinfo@eisai.com

Locations

United States, California

California Clinical Trials Medical Group/Parexel International; Recruiting

Glendale, California, United States, 91206

United States, Texas

Worldwide Clinical Trials; Recruiting

San Antonio, Texas, United States, 78217

Sponsors and Collaborators

Eisai Inc.

More Information

• Responsible Party: Eisai Inc.
• ClinicalTrials.gov Identifier: NCT04231513
• Other Study ID Numbers: E2814-A001-001
• First Posted: January 18, 2020
• Last Update Posted: April 4, 2022
• Last Verified: March 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Eisai Inc.:

E2814; Healthy Participants; Phase 1; Pharmacokinetics; Pharmacodynamics; Immunogenicity