Dose Escalation Trial of CM310 in Patients With Moderate-to-Severe Atopic Dermatitis (AD)

Study Overview
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Brief Summary
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This is a multi-center, randomized, double blind, placebo-controlled multiple dose escalation study to evaluate the safety, tolerance, PK, PD, immunogenicity and preliminary efficacy of subcutaneously CM310 in moderate-severe AD subjects.

Detailed Description
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The study consists of 3 periods, a up-to-4-week Screening Period, a 4-week randomized Treatment Period and a 8-week Safety Follow-up Period.

Official Title
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A Randomized, Double Blind, Placebo-controlled, Multiple Dose Escalation, Phase Ib/IIa Study to Evaluate the Safety, Tolerance, PK, PD, Immunogenicity and Preliminary Efficacy of Subcutaneously CM310 in Moderate-severe AD Subjects.

Conditions
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Moderate-to-severe Atopic Dermatitis

Intervention / Treatment
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* Drug: CM310
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed as AD for at least 12 months before Screening, with below requirements: 1)EASI score ≥16 at Screening and Baseline; 2) IGA score ≥3 (0-5 points scale) at Screening and Baseline; 3) ≥10% BSA of AD involvement at Screening and Baseline; 4) Pruritus NRS average score ≥3 at Baseline. Inadequate response to topical medications. Exclusion Criteria: Not enough washing-out period for previous therapy. Concurrent disease/status which may potentially affect the efficacy/safety judgement. Organ dysfunction. Pregnancy. Other.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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: CM310 75mg arm<br>75mg for 3 doses, every 2 weeks, SC | Drug: CM310<br>* IL-4Rα monoclonal antibody<br>|
| Experimental: CM310 150mg arm<br>150mg for 3 doses, every 2 weeks, SC | Drug: CM310<br>* IL-4Rα monoclonal antibody<br>|
| Experimental: CM310 300mg arm<br>300mg for 3 doses, every 2 weeks, SC | Drug: CM310<br>* IL-4Rα monoclonal antibody<br>|
| Experimental: CM310 600(1st)+300mg(2nd,3rd) arm<br>600mg for 1st dose, and then 300 mg for 2nd and 3rd doses, every 2 weeks, SC | Drug: CM310<br>* IL-4Rα monoclonal antibody<br>|
| Placebo Comparator: placebo arm<br>placebo for 3 doses, every 2 weeks, 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 parameters (e.g., Incidence of AE, abnormal physical examinations, abnormal vital signs, abnormal ECG, and abnormal lab testing) | Incidence of AE, abnormal physical examinations, abnormal vital signs, abnormal ECG, and abnormal lab testing. | Baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics parameter: Peak concentration (Cmax) | Peak concentration (Cmax) | Baseline to Week 12 | 
| Pharmacokinetics parameter: Area under the plasma concentration-time curve from 0 to ∞ (AUC0-∞) | Area under the plasma concentration-time curve from 0 to ∞ (AUC0-∞) | Baseline to Week 12 | 
| Pharmacokinetics 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 to Week 12 | 
| Pharmacokinetics parameter: Clearance rate (CL/F) | Clearance rate (CL/F) | Baseline to Week 12 | 
| Pharmacodynamics parameters: Serum Thymus and activation regulated chemokine (TARC) | Serum Thymus and activation regulated chemokine (TARC), total IgE level and blood eosinophil count (EOS) | Baseline to Week 12 | 
| Pharmacodynamics parameters: Blood eosinophil count (EOS) | Blood eosinophil count (EOS) | Baseline to Week 12 | 
| Pharmacodynamics parameters: Total IgE level | Total IgE level | Baseline to Week 12 | 
| Immunogenicity: Proportion of subjects with anti-drug antibody (ADA) | Proportion of Participants with anti-drug antibody (ADA) | Baseline to Week 12 | 
| Preliminary efficacy: Proportion of subjects with IGA 0 or 1 | Proportion of subjects with Investigator's Global Assessment (IGA, on a 6-point scale, range from 0-5 point, higher scores mean a worse disease severity) 0 or 1 | Baseline to Week 12 | 
| Preliminary efficacy: Proportion of subjects with a reduction of IGA from baseline of ≥ 2 points | Proportion of subjects with a reduction of IGA from baseline of ≥ 2 points | Baseline to Week 12 | 
| Preliminary efficacy: Proportion of subjects with IGA 0 or 1 and a reduction of IGA from baseline of ≥ 2 points | Proportion of subjects with IGA 0 or 1 and a reduction of IGA from baseline of ≥ 2 points | Baseline to Week 12 | 
| Preliminary efficacy: Proportion of subjects with EASI-50 | Proportion of subjects with The Eczema Area and Severity Index(EASI)-50 (≥50 percent improvement from baseline) | Baseline to Week 12 | 
| Preliminary efficacy: Proportion of subjects with EASI-75 | Proportion of subjects with EASI-75 (≥75 percent improvement from baseline) | Baseline to Week 12 | 
| Preliminary efficacy: Proportion of subjects with improvement (reduction) of pruritus NRS from baseline | Proportion of subjects with improvement (reduction) of pruritus Numerical Rating Scale(NRS) from baseline; The range of NRS is from 0 (no itch)-10 (worst imaginable itch) | Baseline to Week 12 |