A Phase 1 Single Dose Study of E6011 in Japanese Healthy Adult Male Subjects (Study E6011-J081-001)

Study Overview
=================
Brief Summary
-----------------
To evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of a single ascending dose (SAD) administration of E6011 in Japanese healthy volunteers.

Official Title
-----------------
A Phase 1 Single Dose Study of E6011 in Japanese Healthy Adult Male Subjects

Conditions
-----------------
Healthy Male Volunteers

Intervention / Treatment
-----------------
* Drug: E6011
* Drug: E6011 Matching Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria; Non-smoking Japanese male subjects aged >= 20 to less than 45 years BMI at screening is >= 18.5 kg/m2 to less than 25.0 kg/m^2 Males who have not had a successful vasectomy and their female partners must agree to practice highly effective contraception throughout the study period. Exclusion criteria; Has been treated with biologic products (except for immunoglobulin preparation) Have received immunoglobulin or blood preparation within 6 months before the study drug administration Received inoculation within 4 weeks before the study drug administration Has a history of autoimmune disease or immunodeficiency Has a clinically significant angioedema, hematemesis, anal hemorrhage, or hemoptysis Has a history of acute myocardial infarction, cerebral infarction, cerebral hemorrhage, or arteriosclerosis obliterate With gross hematuria, occult bleeding in urine (>=1+) and urine protein (>=1+) , or either of (>=2+) at screening Has a clinically significant vasculitis (e.g., multiple mononeuropathy) Known to be positive for human immunodeficiency virus (HIV antigen and antibody), hepatitis B virus surface antigen (HBs antigen), hepatitis B virus surface antibody (HBs antibody), hepatitis B virus (HBV) DNA, hepatitis C virus (HCV) antibody, or syphilis serology test Known to be positive for human T-cell lymphotropic virus type 1 (HTVL-1) antibody at screening Known to be positive for QuantiFERON-TB Gold Test Treated with ethical drug(s) within 4 weeks before the study drug administration (except for disinfectants, eye drops) Treated with non-prescription drug(s) within 2 weeks before the study drug administration (except for disinfectants, eye drops) Has participated in another clinical trial and received an investigational drug or device within 6 months before the study drug administration Received blood transfusion within 1 year, 400 mL or more whole blood donation within 12 weeks, or 200 mL or more whole blood donation within 4 weeks, or blood constituent donation within 2 weeks before the study drug administration.

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 44 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: E6011<br> | Drug: E6011<br>* A single ascending dose (SAD) administration of E6011 is administered to 8 groups as a 30-minute intravenous infusion at a dose of either 0.0006, 0.006, 0.04, 0.2, 1, 3, 6, or 10 mg/kg. Each participant in each group will receive a single-dose only once. The study drug will not be administered to more than two participants on the same day, and the second participant must start the study treatment after at least a 2-hour interval from the start of the study treatment in the first participant. The subsequent ascending dose groups will start approximately at least every 3 weeks following the study treatment in the first participant of each group.<br>|
| Placebo Comparator: E6011 Matching Placebo<br> | Drug: E6011 Matching Placebo<br>* A SAD administration of E6011 Matching Placebo is administered to 2 participants in each of 8 groups as a 30-minute intravenous infusion at a placebo dose of either 0.0006, 0.006, 0.04, 0.2, 1, 3, 6, or 10 mg/kg. Each participant in each group will receive a single-dose only once. The study drug will not be administered to more than two participants on the same day, and the second participant must start the study treatment after at least a 2-hour interval from the start of the study treatment in the first participant. The subsequent ascending E6011 Matching Placebo dose groups will start approximately at least every 3 weeks following the study treatment in the first participant of each group.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events | An Adverse Event (AE) is any untoward medical occurrence in a participant administered an investigational product. An AE does not necessarily have a causal relationship with the medicinal product. The investigator or sub-investigator reviews all laboratory findings and determines if they constitute an AE. In-patient observation assessments will be performed during 1 week post-dose, followed by the out-patient observation assessments in groups: 0.0006, 0.006, 0.04, 0.2 mg/kg up to the end of Week 8 and in groups: 1, 3, 6, 10 kg/mg) up to the end of Week 24. | Up to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) |  | Up to 24 Weeks post-dose | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) |  | Up to 24 Weeks post-dose | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)] | AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t). | Up to 24 Weeks post-dose | 
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - infinity)] | AUC (0 - infinity)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - infinity). It is obtained from AUC (0 - t) plus AUC (t - infinity). | Up to 24 Weeks post-dose | 
| Plasma Decay Half-Life (t1/2) | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | Up to 24 Weeks post-dose | 
| Pharmacokinetic Parameter: Volume of Distribution (Vd) |  | Up to 24 Weeks post-dose | 
| Pharmacokinetic Parameter: Clearance (CL) |  | Up to 24 Weeks post-dose | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Healthy volunteers, immunogenicity, anti-E6011 antibody