Single Ascending Dose Study of CM338 in Healthy Volunteers

Study Overview
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Brief Summary
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This study was a single-center, randomized, double blind, placebo-controlled, single-dose, dose-increasing study to evaluate the safety, tolerability, PK characteristics, PD effect, and immunogenicity of CM338 injection administered intravenously or subcutaneously at different doses in healthy subjects.

Detailed Description
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The study included screening period, baseline period, administration and hospitalization observation period, and safety follow-up period. Sixty-six healthy volunteers will be enrolled and randomized into 8 groups.

Official Title
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A Single-dose, Randomized, Double Blind, Placebo-controlled, Dose-increasing Study to Evaluate the Safety, Tolerability, PK Characteristics, PD Effect, and Immunogenicity of CM338 Injection in Healthy Subjects.

Conditions
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Healthy

Intervention / Treatment
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* Drug: CM338
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: with the ability to understand this study and voluntarily sign the informed consent form. 18 to 65 years of age. with normal or abnormal without clinically significance on medical history, vital signs, physical examination, 12-lead ECG, laboratory examination, chest X-ray, and abdominal color ultrasound, etc. able to communicate with the researchers and follow the requirements specified in the protocol. agree to use effective contraceptive methods from signing the ICF to 6 months after the administration. Exclusion Criteria: plan to conduct any major surgery during the study. known allergy to monoclonal antibody drugs or other related drugs, or to the excipients of CM338 injection. with any clinical history including serious diseases or circulatory system, endocrine system, nervous system, blood system, immune system, mental system and metabolic abnormalities.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CM338 30mg, IV<br>30mg, single dose, IV | Drug: CM338<br>* CM338 : a humanized monoclonal antibody.<br>|
| Experimental: CM338 60mg, IV<br>60mg, single dose, IV | Drug: CM338<br>* CM338 : a humanized monoclonal antibody.<br>|
| Experimental: CM338 120mg, IV<br>120mg, single dose, IV | Drug: CM338<br>* CM338 : a humanized monoclonal antibody.<br>|
| Experimental: CM338 240mg, IV<br>240mg, single dose, IV | Drug: CM338<br>* CM338 : a humanized monoclonal antibody.<br>|
| Experimental: CM338 240mg, SC<br>240mg, single dose, SC | Drug: CM338<br>* CM338 : a humanized monoclonal antibody.<br>|
| Experimental: CM338 480mg, IV<br>480mg, single dose, IV | Drug: CM338<br>* CM338 : a humanized monoclonal antibody.<br>|
| Experimental: CM338 600mg, IV<br>600mg, single dose, IV | Drug: CM338<br>* CM338 : a humanized monoclonal antibody.<br>|
| Experimental: CM338 600mg, SC<br>600mg, single dose, SC | Drug: CM338<br>* CM338 : a humanized monoclonal antibody.<br>|
| Placebo Comparator: Placebo<br>Placebo, single dose, IV or SC | Drug: Placebo<br>* Placebo.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety : Incidence of Adverse Events (AEs). | Incidence of AEs, including any abnormal physical examinations, abnormal vital signs, abnormal ECG, and abnormal lab testing. | Baseline up to Day 57 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) parameter : Peak Plasma concentration (Cmax) | Peak Plasma concentration (Cmax) | Baseline up to Day 57 | 
| Pharmacokinetics (PK) parameter : Time to reach peak concentration (Tmax) | Time to reach peak concentration (Tmax) | Baseline up to Day 57 | 
| Pharmacokinetics (PK) parameter : Area under the plasma concentration-time curve from 0 to ∞ (AUC0-∞) | Area under the plasma concentration-time curve from 0 to ∞ (AUC0-∞) | Baseline up to Day 57 | 
| Pharmacokinetics (PK) parameter : Area under the plasma concentration-time curve from 0 to t (AUC0-t) | Area under the plasma concentration-time curve from 0 to t (AUC0-t) | Baseline up to Day 57 | 
| Pharmacokinetics (PK) parameter : Clearance rate (CL/F) | Clearance rate (CL/F) | Baseline up to Day 57 | 
| Bioavailability : bioavailability of CM338 with SC | The bioavailability of CM338 with SC | Baseline up to Day 57 | 
| Pharmacodynamics (PD) : C4b deposition activity of mannose-binding lectin serine protease 2 (MASP-2) in serum. | C4b deposition activity of mannose-binding lectin serine protease 2 (MASP-2) in serum. | Baseline up to Day 57 | 
| Pharmacodynamics (PD) : the content of mannose-binding lectin serine protease 2 (MASP-2) in serum. | The content of mannose-binding lectin serine protease 2 (MASP-2) in serum. | Baseline up to Day 57 | 
| Immunogenicity: Proportion of subjects with anti-drug antibody (ADA). | Proportion of subjects with anti-drug antibody (ADA). | Baseline up to Day 57 |