A Study of NBL-012 in Healthy Chinese Subjects

Study Overview
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Brief Summary
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This is a phase 1, randomized, double-blind, placebo-controlled, sequential cohort study to evaluate the safety, tolerability and pharmacokinetics (PK) of NBL-012 as single ascending doses (SAD) administered subcutaneously to healthy Chinese subjects.

Detailed Description
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This is a phase 1, randomized, double-blind, placebo-controlled, sequential cohort study to evaluate the safety, tolerability and pharmacokinetics of NBL-012 administered subcutaneously as single ascending doses (SAD) to healthy Chinese subjects. Six dose cohorts will be intended for enrollment. The first dose will be sentinel group which will consist of 2 subjects, both of whom will receive active NBL-012. For subsequent dose cohorts, subjects will be given a single escalating SC dose of NBL-01

Official Title
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A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of NBL-012 in Healthy Chinese Subjects

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: NBL-012 Injection
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and/or female subjects between the ages of 18 and 45 years (inclusive) at screening. Body Mass Index (BMI) of 18 to 26 kg/m2 (inclusive), body weight for male ≥50 kg and for female≥45 kg. Good general health defined as no clinically significant abnormalities identified by a detailed medical history (thoracic and abdominal examination, nervous and mental system examination, etc.), full physical examination, including blood pressure and pulse rate measurement, 12-lead ECG, Exclusion Criteria: Participated in any drug or medical device clinical trial within 3 months before screening Pregnant or nursing (lactating) women who have a positive blood/urine pregnancy test. Females of child-bearing potential (defined as all females physiologically capable of becoming pregnant) and males who are unwilling or unable to use effective contraception during the study and until the end of study visit (more than 15 weeks after drug administration), or subjects with a plan to give birth wi

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NBL-012 Injection<br>Two subjects will be enrolled in the initial dose. 8 out of 10 healthy subjects will be randomized to receive a single dose of NBL-012 Injection for subsequent dose cohorts | Drug: NBL-012 Injection<br>* a single subcutaneous injection<br>|
| Placebo Comparator: Placebo<br>2 out of 10 healthy subjects will be randomized to receive a single dose of placebo. | Drug: Placebo<br>* a single subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 | Number of participants with treatment-related adverse events will be assessed by CTCAE v5.0. The AEs will be summarized according to the system organ class (SOC) and preferred term (PT), including the number and percentage of participants who had AEs. | Up to Day 113 from screening | 
| Clinically significant changes from baseline in 12-lead electrocardiogram (ECG) examination will be recorded as AEs at each visit time point. | ECG monitoring includes heart rate in bpm. | Up to Day 113 from screening | 
| Clinically significant changes from baseline in 12-lead electrocardiogram (ECG) examination will be recorded as AEs at each visit time point. | ECG monitoring includes P-R, QT and QTc intervals in ms. | Up to Day 113 from screening | 
| Clinically significant changes from baseline in physical examination will be recorded as AEs at each visit time point. | Physical examination includes general conditions, skin, neck, chest, spine, limbs, nervous system, and lymphatic system. | Up to Day 113 from screening | 
| Clinically significant changes from baseline in vital signs examination will be recorded as AEs at each visit time point. | Vital signs monitoring includes body temperature in degrees Celsius. | Up to Day 113 from screening | 
| Clinically significant changes from baseline in vital signs examination will be recorded as AEs at each visit time point. | Vital signs monitoring includes respiratory rate and pulse in times per minute. | Up to Day 113 from screening | 
| Clinically significant changes from baseline in vital signs examination will be recorded as AEs at each visit time point. | Vital signs monitoring includes systolic blood pressure and diastolic blood pressure in mmHg. | Up to Day 113 from screening | 
| Clinically significant changes from baseline in routine blood test will be recorded as AEs at each visit time point. | Routine blood test includes white blood cell count, platelet, neutrophilic granulocyte count, lymphocyte count and monocyte count in 10^9 /L. | Up to Day 113 from screening | 
| Clinically significant changes from baseline in blood biochemistry test will be recorded as AEs at each visit time point. | Blood biochemistry test includes alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and glutamyltranspeptidase in U/L. | Up to Day 113 from screening | 
| Clinically significant changes from baseline in routine urine test will be recorded as AEs at each visit time point. | Routine urine test includes glucose and protein in mg/dL. | Up to Day 113 from screening | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak plasma concentration (Cmax) of NBL-012 injection |  | Pre-dose and multiple timepoints up to 113 days post-dose | 
| Area under the plasma concentration versus time curve (AUC) of NBL-012 injection |  | Pre-dose and multiple timepoints up to 113 days post-dose | 
| Time to achieve maximum plasma concentration (Tmax) of NBL-012 injection |  | Pre-dose and multiple timepoints up to 113 days post-dose | 
| Apparent clearance(CL/F) of NBL-012 injection |  | Pre-dose and multiple timepoints up to 113 days post-dose | 
| Apparent volume of Distribution(Vz/F) of NBL-012 injection |  | Pre-dose and multiple timepoints up to 113 days post-dose | 
| Half-life(t1/2) of NBL-012 injection |  | Pre-dose and multiple timepoints up to 113 days post-dose | 
| The incidence of Anti-drug antibody (ADA) | The incidence of Anti-drug antibody (ADA) | Pre-dose and multiple timepoints up to 113 days post-dose | 
| Free IL-23 concentration in Serum. | Free IL-23 concentration in Serum. | Pre-dose and multiple timepoints up to 113 days post-dose |