Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of a Single Ascending Dose (SAD) of CAN106 Administered Intravenously (IV) in Healthy Subjects

Study Overview
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Brief Summary
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This is a single site, single dose escalation study in healthy subject with CAN106. The study is to assess the safety and tolerability of single escalating doses of CAN106; to characterize the PK and PD profile of CAN106; and to evaluate the immunogenicity of CAN106 injection.

Official Title
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Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of a Single Ascending Dose (SAD) of CAN106 Administered Intravenously (IV) in Healthy Subjects

Conditions
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PNH

Intervention / Treatment
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* Drug: CAN106
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must be able to understand and provide informed consent. Males or females, between 21 and 45 years of age, inclusive; Body mass index must be within the range of 18.5 to 32.0 kg/m2; 12-lead electrocardiogram (ECG) within normal limits with no clinically significant abnormalities in the opinion of the Investigator； Systolic blood pressure ≤140 mmHg and a diastolic blood pressure of ≤ 90 mmHg after 5 minutes with supine rest； non-pregnancy meningococcal vaccinations for at least 2 weeks before dosing Exclusion Criteria: Disease or conditions interfere with participating the trial Active serious mental illness or psychiatric disorder clinically relevant abnormal test results in hepatic function unacceptable CBC lab test asymptomatic complement deficiency Any other clinical safety laboratory test HIV, HBV, HCV positive Alcohol and drug abuse etc.

Ages Eligible for Study
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Minimum Age: 21 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Ascending Dose (SAD)<br>In the SAD arm subjects will be sequentially included in one of up to six cohorts (dose levels). Additional subjects may be added in any cohort if necessary. | Drug: CAN106<br>* CAN106 is a selective inhibitor of complement activation, which binds to the complement component C5.<br>|
| Placebo Comparator: placebo<br>In the SAD arm subjects will be sequentially included in one of up to six cohorts (dose levels). In higher dose levels, subjects will be randomized to receive the treatment or placebo. | Drug: Placebo<br>* placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of subjects with dose-limiting toxicity (DLTs) | TEAEs will be categorized as per the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0 criteria. a DLT is defined as one subject with a Grade 3 AE or higher, that are assessed as drug-related by the site investigator. | 6-months after dosing | 
| Incidence of adverse events (AEs) | An AE is defined as any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. | 6-months after dosing | 
| Incidence of severe adverse events (SAEs) | Any untoward medical occurrence that at any dose: Results in death, Is life-threatening, Requires inpatient hospitalization or prolongation of existing hospitalization, Results in persistent or significant disability/incapacity, or Is a congenital anomaly/birth defect. (ICH E6 (R2)) | 6-months after dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK parameters - tmax | time to reach maximum of concentration (days) | 6-months after dosing | 
| PK parameters-Cmax | peak plasma concentration | 6-months after dosing | 
| PK parameters - AUC0-t | Area under the plasma concentration versus time curve to the last visit (AUCt) | 6-months after dosing | 
| PK parameters - t1/2 | terminal elimination half-life | 6-months after dosing | 
| PD endpoints-free C5 | maximal change from baseline in free C5 concentrations at each of scheduled post baseline assessment time-points (µg/ml); | 6-months after dosing | 
| PD endpoints-CH50 | maximal change from baseline total complement activity (CH50) at each of scheduled post baseline assessment time-points (%); | 6-months after dosing | 
| PD endpoints-total C5 | meausure the absolute change from baseline in total C5 concentrations at each of scheduled post baseline assessment time-points (µg/ml); | 6-months after dosing | 
| Immunogenicity | Anti-drug Antibody (ADA) titers | 6-months after dosing |