A Study to Evaluate the PK Similarity of AK104 in Healthy Chinese Male Subjects

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the pharmacokinetic similarity of AK104 with different manufacturing process in healthy male subjects. Another purpose is to determine safety, and immunogenicity of AK104 with different manufacturing process.

Official Title
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A Phase I Study to Evaluate the Similarity of Pharmacokinetic (PK) in AK104 (a PD-1/CTLA-4 Bispecific Antibody) With Different Manufacturing Process in Healthy Chinese Male Subjects

Conditions
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Healthy Male Subjects

Intervention / Treatment
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* Drug: AK104 (before the change)
* Drug: AK104 (after the change)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males aged 18 to 45; Body Mass Index (BMI) is 19.0 28.0 kg/m2, and body weight is 50.0 80.0kg ; Signing informed consent form before the trial and having a full understanding of the trial content, process and possible adverse reactions; Able to complete the study according to the requirements of the study protocol. Exclusion Criteria: Those with a history of digestive tract, respiratory, cardiovascular, endocrine, urinary, neurological, hematological, metabolic and other systemic diseases; Those with a history of autoimmune diseases; Those with a history of malignant tumor, unless it is a skin squamous cell carcinoma, basal cell carcinoma or cervical cancer in situ that has been successfully resected and has no evidence of metastasis; Regular drinkers within 6 months prior to screening; Those who are suspected or confirmed to be allergic or have had severe drug or food allergy reactions in the past, have a clear history of allergies and/or are allergic to the study drug or its components after inquiries; Those who have used anti-PD-1/PD-L1 or/and anti-CTLA-4 drugs in the past; Those who have been vaccinated with live or attenuated-live vaccines within 3 months before screening, or who are expected to receive vaccines during the study period; Those who lost blood, donated blood or received any blood product transfusion of ≥400 ml within 3 months before screening; Those who received major surgery or hospitalization due to illness within 3 months before screening; Abnormal laboratory tests with clinical significance at screening; Positive drug screening result; Have a childbirth plan within 6 months from the screening period to the trial drug administration, or who are unwilling to take the contraceptive measures specified in the protocol during the trial period.

Ages Eligible for Study
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Minimum Age: 18 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AK104 (after the change)<br>Drug: AK104 (after the change) Dose 1 and dose 2, will be administrated intravenously in 60±10 minutes. | Drug: AK104 (after the change)<br>* Dose 1 and dose 2 in pilot study, and recommended dose in pivotal study.<br>|
| Active Comparator: AK104 (before the change)<br>Drug: AK104 (before the change) Dose 1 and dose 2, will be administrated intravenously in 60±10 minutes. | Drug: AK104 (before the change)<br>* Dose 1 and dose 2 in pilot study, and recommended dose in pivotal study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pilot study: Adverse Events (AEs) | An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. | Up to day 30 | 
| Pivotal study: Area under the plasma concentration-time curve (AUC0-infinity) |  | From pre-dose to day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration-time curve (AUC0-t) |  | From pre-dose to day 29 | 
| Maximum plasma concentration (Cmax) |  | From pre-dose to day 29 | 
| Volume of distribution (Vd) |  | From pre-dose to day 29 | 
| Clearance (CL) |  | From pre-dose to day 29 | 
| Ratio of AUC0-t/AUC0-infinity |  | From pre-dose to day 29 | 
| Time to maximum concentration (Tmax) |  | From pre-dose to day 29 | 
| Half-life (t1/2) |  | From pre-dose to day 29 | 
| Anti-drug Antibody (ADA) | Number and percentage of subjects with detectable ADA | From pre-dose to day 29 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AK104