Single Ascending Dose Study to Assess the Safety, Tolerability, PK and PD of ONO-4685 in Japanese and Caucasian Healthy Adult Male Subjects

Study Overview
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Brief Summary
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To investigate safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity in Japanese and Caucasian healthy adult male subjects when ONO-4685 is administered as a single-dose by intravenous infusion.

Detailed Description
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To investigate safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity when ONO-4685 is administered by single-dose intravenous continuous infusion in Japanese and Caucasian healthy adult male subjects. In addition, in Japanese healthy adult male subjects, to investigate dosing condition of Keyhole limpet hemocyanin (KLH) and to investigate safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity when ONO-4685 is administered by single-dose intravenous continuous infusion after treating with KLH.

Official Title
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Single Ascending Dose Study to Assess the Safety, Tolerability, PK and PD of ONO-4685 in Japanese and Caucasian Healthy Adult Male Subjects

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Biological: ONO-4685
* Biological: Placebo
* Biological: KLH
* Biological: KLH, ONO-4685
* Biological: KLH, placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Japanese healthy adult male subjects (PartA, B, and C) Caucasian healthy adult male subjects (Part D) Age (at the time of informed consent): ≥20 yeas, ≤ 45 yeas Body weight (at the time of screening test): ≥50 kg Exclusion Criteria: Subjects who are on a treatment for or with a history of respiratory, cardiovascular, psychiatric, neurologic, gastrointestinal, immunologic, hepatic, renal, hematopoietic or endocrine and/or other disease. Subjects with current or with a history of severe allergy to drugs or foods Subjects with current or with a history of drug or alcohol abuse

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ONO-4685 (PartA, D)<br> | Biological: ONO-4685<br>* Single ascending dose of ONO-4685 will be administered by intravenous continuous infusion at the designated speed.<br>|
| Placebo Comparator: Placebo (PartA, D)<br> | Biological: Placebo<br>* Placebo will be administered by intravenous continuous infusion at the designated speed.<br>|
| Experimental: KLH+placebo (Part B)<br> | Biological: KLH<br>* KLH 1 mg per dose will be subcutaneously administered. In addition, all subjects will be administered placebo after KLH administration.<br>|
| Experimental: KLH+ONO-4685 (PartC)<br> | Biological: KLH, ONO-4685<br>* Part C will be conducted in a study design that ONO-4685 will be administered within the dose range, for which the safety has been confirmed in Part A, after administering KLH in the dose regimens selected according to the investigation result in Part B.<br>|
| Experimental: KLH+placebo (PartC)<br> | Biological: KLH, placebo<br>* Part C will be conducted in a study design that placebo will be administered within the dose range, for which the safety has been confirmed in Part A, after administering KLH in the dose resimens selected according to the investigation result in Part B.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events [Safety and Tolerability] | Number of participants with adverse events as assessed by CTCAE v5.0 | Up to 84 days | 
| Vital sign [Safety and Tolerability] | Summary statistics of blood pressure/pulse rate, respiratory rate, SpO2 | Up to 84 days | 
| Body temperature [Safety and Tolerability] | Summary statistics of body temperature | Up to 84 days | 
| Body weight [Safety and Tolerability] | Summary statistics of body weight | Up to 84 days | 
| ECG parameter test [Safety and Tolerability] | Summary statistics of ECG parameter test (Heart Rate, RR, PR, QRS, QT, and QTcF) | Up to 84 days | 
| Laboratory test [Safety and Tolerability] | Summary statistics of laboratory test (hematologic test, blood biochemistry test, blood coagulation test, immunoserologic test urinalysis) | Up to 84 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax [Pharmacokinetic] (PartA, C, and D) | Assessment of the Cmax of ONO-4685 | Up to 84 days | 
| Tmax [Pharmacokinetic] (PartA, C, and D) | Assessment of the Tmax of ONO-4685 | Up to 84 days | 
| AUC [Pharmacokinetic] (PartA, C, and D) | Assessment of the AUC168h, AUClast, and AUCinf of ONO-4685 | Up to 84 days | 
| T1/2 [Pharmacokinetic] (PartA, C, and D) | Assessment of the T1/2 of ONO-4685 | Up to 84 days | 
| CL [Pharmacokinetic] (PartA, C, and D) | Assessment of the CL of ONO-4685 | Up to 84 days | 
| Vss [Pharmacokinetic] (PartA, C, and D) | Assessment of the Vss of ONO-4685 | Up to 84 days | 
| Serum cytokine concentration [Pharmacodynamics] (PartA, C, and D) | Serum cytokine concentration | Up to 84 days | 
| Hemocyte test [Pharmacodynamics] (PartA, C, and D) | Hemocyte test | Up to 84 days | 
| Pharmacodynamics (Part B and C) | Anti-KLH antibody | Up to 84 days | 
| Immunogenicity (PartA, C, and D) | Anti-ONO-4685 antibody | Up to 84 days |