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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04231513
Recruitment Status : Recruiting
First Posted : January 18, 2020
Last Update Posted : April 4, 2022
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.

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.

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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

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.




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 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04231513


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

Locations
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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.
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Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT04231513    
Other Study ID Numbers: E2814-A001-001
First Posted: January 18, 2020    Key Record Dates
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/.

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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