Subcutaneously CM310/Placebo in Patients With Moderate-to-Severe Atopic Dermatitis (AD)

Study Overview
=================
Brief Summary
-----------------
This is a multi-center, randomized, double blind, placebo-controlled phase IIb study to evaluate the efficacy, safety, PK, PD and immunogenicity of CM310 in moderate-severe AD subjects. The study consists of 3 periods, a up-to-4-week Screening Period, a 16-week randomized Treatment Period and a 8-week Safety Follow-up Period.

Detailed Description
-----------------
Subjects will be required to apply moisturizers after ICF signed and continue throughout the study.

Official Title
-----------------
A Randomized, Double Blind, Placebo-Controlled Phase IIb Study to Evaluate the Efficacy and Safety of CM310 Recombinant Humanized Monoclonal Antibody Injection in Patients With Moderate-to-Severe Atopic Dermatitis (AD)

Conditions
-----------------
Moderate-to-severe Atopic Dermatitis

Intervention / Treatment
-----------------
* Biological: CM310
* Biological: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High-dose arm<br>600mg for 1st dose, and then 300 mg for 2-8nd doses, every 2 weeks, SC | Biological: CM310<br>* IL-4Rα monoclonal antibody<br>|
| Experimental: low-dose arm<br>300mg for 1st dose, and then 150 mg for 2-8nd doses, every 2 weeks, SC | Biological: CM310<br>* IL-4Rα monoclonal antibody<br>|
| Placebo Comparator: placebo<br>placebo for 1-8 doses, every 2 weeks, SC | Biological: Placebo<br>* Placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EASI-75 | Proportion of subjects with EASI-75 (≥75 percent improvement from baseline) | at Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigator's Global Assessment (IGA) 0/1 | Proportion of subjects with IGA 0 or 1 (on a 6-point scale, range from 0-5 point, higher scores mean a worse disease severity) and a reduction from baseline of ≥2 points. | at week 16 | 
| reduction of IGA from baseline of ≥ 2 points | Proportion of subjects with IGA 0 or 1 (on a 6-point scale, range from 0-5 point, higher scores mean a worse disease severity) and a reduction from baseline of ≥2 points. | at week 16 | 
| The Eczema Area and Severity Index (EASI)-90 | Proportion of subjects with EASI-90 (≥90 percent improvement from baseline) | at week 16 | 
| The Eczema Area and Severity Index (EASI)-50 | Proportion of subjects with EASI-50 (≥50 percent improvement from baseline) | at week 16 | 
| Improvement of Numerical Rating Scale (NRS) | Proportion of subjects with improvement (reduction) of pruritus NRS of ≥4 points from baseline. The range of NRS is from 0 (no itch)-10 (worst imaginable itch). | at week 16 | 
| Body Surface Area (BSA) | Change from baseline in percent of BSA | Baseline to Week 24 | 
| Dermatology Life Quality Index (DLQI) | Change from baseline in DLQI | Baseline to Week 24 | 
| Safety parameters | Incidence of AE, abnormal physical examinations, abnormal vital signs, abnormal ECG, and abnormal lab testing. | Baseline to Week 24 | 
| Pharmacokinetics parameters | trough concentration and exposure of CM310 | Baseline to Week 24 | 
| Pharmacodynamics | Serum Thymus and activation regulated chemokine (TARC) | Baseline to Week 24 | 
| Pharmacodynamics | Total IgE level | Baseline to Week 24 | 
| immunogenicity | Detection of anti-drug antibody (ADA) | Baseline to Week 24 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Atopic dermatitis