A Phase I Clinical Trial of AK115 in Healthy Subjects

Study Overview
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Brief Summary
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This trial is a randomized, double-blind, placebo-controlled dose escalation phase I trial following single dose subcutaneous administration of AK115 injection. It aims to evaluate the safety, pharmacokinetic characteristics, pharmacodynamic effect and immunogenicity of single dose of AK115 injection in healthy subjects.

Official Title
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A Phase I Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Characteristics of Single Dose Subcutaneous Administration of AK115 in Healthy Subjects

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: AK115
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1) The subjects fully understand the purpose, content, process and possible adverse reactions of the trial, voluntarily participate in the trial, and sign the informed consent before any test procedure; 2) Healthy male and female subjects aged 18-55 years (including 18 and 55 years); 3) Male weight ≥ 50.0kg, female weight ≥ 45.0kg; Body mass index (BMI) = body weight (kg) / height 2 (M2), in the range of 19.0   26.0kg/m2 (including the critical value); 4) The blood pregnancy test results of female subjects of chidbearing potential during the screening period were negative. During the whole trial period and within 84 days after receiving the inveatigational drug, the subjects and their partners voluntarily take effective contraceptive measures specified in the protocol. Female subjects without childbearing potential need to meet the standards specified in the protocol, 5) The subjects can communicate well with the researchers, understand and comply with the requirements of this trial protocol. Exclusion Criteria: Allergic to ak115 component and any monoclonal antibody, or have a history of allergies of 3 or more kinds food or drugs ; There are accompanying diseases , or previous serious and chronic diseases and those who have not been cured; The results of physical examination, laboratory examination or ECG examination in the screening period are judged by the researcher to be abnormal and clinically significant; Have a history of transplantation of important organs; Abnormal liver and kidney functions and blood routine, refer to the protocol Hepatitis B surface antigen, hepatitis C antibody, HIV antigen antibody, Treponema pallidum antibody positive; History of alcohol abuse or Drug abusers within 12 months before screening or those with positive urine drug screening results during screening; Blood donation or massive blood loss (> 400ml) or Smoking more than 5 cigarettes per day within 3 months before check-in; Female subjects are in pregnancy or lactation; Use of medications including over-the-counter medication within 14 days before the investigational drug; Participated in the clinical trial of any trial drug within 3 months before the investigational drug or still within 5 half lives of other trial drugs (whichever is longer); Subjects who received monoclonal antibodies or other biological agents within 3 months before investigational drug; Subjects who had received systemic corticosteroids 12 months before screening; Any conditions which, in the opinion of the Investigator, would make the subject unsuitable for enrollment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

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: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 0.5mg AK115 SC<br> | Drug: AK115<br>* Abdominal subcutaneous injection<br>|
| Experimental: 1mg AK115or placebo SC<br> | Drug: AK115<br>* Abdominal subcutaneous injection<br>Drug: Placebo<br>* Abdominal subcutaneous injection<br>|
| Experimental: 3mg AK115or placebo SC<br> | Drug: AK115<br>* Abdominal subcutaneous injection<br>Drug: Placebo<br>* Abdominal subcutaneous injection<br>|
| Experimental: 10mg AK115or placebo SC<br> | Drug: AK115<br>* Abdominal subcutaneous injection<br>Drug: Placebo<br>* Abdominal subcutaneous injection<br>|
| Experimental: 30mg AK115or placebo SC<br> | Drug: AK115<br>* Abdominal subcutaneous injection<br>Drug: Placebo<br>* Abdominal subcutaneous injection<br>|
| Experimental: 60mg AK115or placebo SC<br> | Drug: AK115<br>* Abdominal subcutaneous injection<br>Drug: Placebo<br>* Abdominal subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity classification of adverse events | Incidence and severity classification of adverse events | 0-12week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameters of AK115 in healthy subjects | Pharmacokinetic parameters of AK115 in healthy subjects: peak concentration (Cmax) | 0-12week | 
| Pharmacokinetic parameters of AK115 in healthy subjects | Pharmacokinetic parameters of AK115 in healthy subjects: time to peak (Tmax) | 0-12week | 
| Pharmacokinetic parameters of AK115 in healthy subjects | Pharmacokinetic parameters of AK115 in healthy subjects: apparent terminal elimination rate constant（ λ z) | 0-12week | 
| Pharmacokinetic parameters of AK115 in healthy subjects | Pharmacokinetic parameters of AK115 in healthy subjects: Area under drug time curve (AUC) | 0-12week | 
| Pharmacokinetic parameters of AK115 in healthy subjects | Pharmacokinetic parameters of AK115 in healthy subjects: apparent total body clearance (CL / F) | 0-12week | 
| Pharmacokinetic parameters of AK115 in healthy subjects | Pharmacokinetic parameters of AK115 in healthy subjects: apparent distribution volume (VZ / F) | 0-12week | 
| Pharmacokinetic parameters of AK115 in healthy subjects | Pharmacokinetic parameters of AK115 in healthy subjects: elimination half-life (T1 / 2) | 0-12week | 
| Pharmacokinetic parameters of AK115 in healthy subjects | Pharmacokinetic parameters of AK115 in healthy subjects: mean residence time (MRT), etc | 0-12week | 
| Changes in serum total nerve growth factor (NGF) levels from baseline. | Changes in serum total nerve growth factor (NGF) levels from baseline. | 0-12 week | 
| Immunogenicity characteristics: the number and percentage of anti AK115 antibody (ADA) | Immunogenicity characteristics: the number and percentage of anti AK115 antibody (ADA) | 0-12week | 
| Immunogenicity characteristics: the number and percentage of neutralizing antibody (NAB) positive subjects | Immunogenicity characteristics: the number and percentage of neutralizing antibody (NAB) positive subjects | 0-12week | 
| Immunogenicity characteristics: time to ADA positive | Immunogenicity characteristics: time to ADA positive | 0-12week |