The Study of CM326 in Patients With Moderate-to-severe Atopic Dermatitis

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 CM326 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 12-week randomized Treatment Period and a 12-week Safety Follow-up Period.

Official Title
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A Randomized, Double Blind, Placebo-Controlled, Multiple Dose Escalation, Phase 2 Study to Evaluate the Safety, Tolerance, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Preliminary Efficacy of CM326 in Patients With Moderate-severe Atopic Dermatitis Subjects

Conditions
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Moderate-to-severe Atopic Dermatitis

Intervention / Treatment
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* Biological: CM326
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: With confirmed Atopic Dermatitis (AD) at least 12 months before the screening Eczema Area and Severity Index (EASI) score ≥16 at screening and baseline Investigator's Global Assessment (IGA) score ≥3 at screening and baseline Body Surface Area (BSA) of involvement of atopic dermatitis ≥10% at screening and baseline The weekly mean score of daily peaks in pruritus NRS at baseline ≥4 Provide signed informed consent Exclusion Criteria: Not enough washing-out period for previous therapy. Presence of other concomitant and poorly controlled serious diseases or recurrent chronic diseases, including but not limited to active infections, cardiovascular and cerebrovascular diseases, pulmonary tuberculosis or other pathogen infections, diabetes mellitus, autoimmune diseases, human immunodeficiency virus (HIV) infection, active hepatitis B, hepatitis C or parasitosis, neoplasm malignant, etc. Patients with severe hepatic or renal impairment, characterized by aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level > 2 times of upper limit of normal (ULN), total bilirubin >1.5 times of upper limit of normal (ULN) or serum creatinine level > upper limit of normal (ULN). Womens who are pregnant or breastfeeding, or who plan to become pregnant during the study.

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: CM326 55 mg, once every two weeks (Q2W)<br>55mg for 6 doses, every 2 weeks, subcutaneous (SC) | Biological: CM326<br>* CM326 injection<br>|
| Experimental: CM326 110 mg, once every two weeks (Q2W)<br>110mg for 6 doses, every 2 weeks, subcutaneous (SC) | Biological: CM326<br>* CM326 injection<br>|
| Experimental: CM326 110 mg, once every four weeks (Q4W)<br>110mg for 3 doses, every 4 weeks, subcutaneous (SC) | Biological: CM326<br>* CM326 injection<br>|
| Experimental: CM326 220 mg, once every two weeks (Q2W)<br>220mg for 6 doses, every 2 weeks, subcutaneous (SC) | Biological: CM326<br>* CM326 injection<br>|
| Experimental: CM326 220 mg, once every four weeks (Q4W)<br>220mg for 3 doses, every 4 weeks, subcutaneous (SC) | Biological: CM326<br>* CM326 injection<br>|
| Placebo Comparator: Placebo<br>Placebo for 6 doses, every 2 weeks, subcutaneous (SC) and placebo for 3 doses, every 4 weeks, subcutaneous (SC) | Other: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events (AE) | Incidence of AEs, including any abnormal physical examinations, abnormal vital signs, abnormal ECG, and abnormal lab testing. | Up to week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) parameter: Time to reach peak concentration (Tmax) | Time to reach peak concentration (Tmax) | Up to Week 24 | 
| Pharmacokinetics (PK) parameter : Peak Plasma concentration (Cmax) | Peak Plasma concentration (Cmax) | Up to Week 24 | 
| Pharmacokinetics (PK) parameter : Area under the plasma concentration-time curve (AUC) | Area under the plasma concentration-time curve (AUC) | Up to Week 24 | 
| Pharmacokinetics (PK) parameter : Clearance rate (CL/F) | Clearance rate (CL/F) | Up to Week 24 | 
| Pharmacokinetics (PK) parameter : Elimination half life (T1/2z) | Elimination half life (T1/2z) | Up to Week 24 | 
| Pharmacodynamics (PD): Changes from baseline in serum thymus activation regulation chemokine (TARC) concentration after CM326 administration | Changes from baseline in serum thymus activation regulation chemokine (TARC) concentration after CM326 administration | Up to Week 24 | 
| Pharmacodynamics (PD): Changes from baseline in eosinophil count after CM326 administration | Changes from baseline in eosinophil count after CM326 administration | Up to Week 24 | 
| Pharmacodynamics (PD): Changes from baseline in serum total immunoglobulin E (IgE) concentration after CM326 administration | Changes from baseline in serum total immunoglobulin E (IgE) concentration after CM326 administration | Up to Week 24 | 
| Pharmacodynamics (PD): Changes from baseline in plasma interleukin-5 (IL-5) concentration after CM326 administration | Changes from baseline in plasma interleukin-5 (IL-5) concentration after CM326 administration | Up to Week 24 | 
| Pharmacodynamics (PD): Changes from baseline in plasma interleukin-13 (IL-13) concentration after CM326 administration | Changes from baseline in plasma interleukin-13 (IL-13) concentration after CM326 administration | Up to Week 24 | 
| Pharmacodynamics (PD): Changes from baseline in serum periostin concentration after CM326 administration | Changes from baseline in serum periostin concentration after CM326 administration | Up to Week 24 | 
| Immunogenicity: anti-drug antibody (ADA) and neutralizing antibody (Nab) | Detection of anti-drug antibody (ADA) and neutralizing antibody (Nab) | Up to Week 24 | 
| Proportion of patients with Investigator's Global Assessment (IGA) score = 0-1 at each visit | IGA is a 6-point scale ranging from 0 (clear) to 5 (very severe) | Up to Week 24 | 
| Proportion of patients with IGA reduction from baseline of ≥2 points at each visit | IGA is a 6-point scale ranging from 0 (clear) to 5 (very severe) | Up to Week 24 | 
| Proportion of patients with Eczema Area and Severity Index (EASI)-50 (≥50 percent reduction in EASI scores from baseline) at each visit | The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 to 72 points, with the higher scores reflecting the worse severity of AD | Up to Week 24 | 
| Proportion of patients with Eczema Area and Severity Index (EASI)-75 (≥75 percent reduction in EASI scores from baseline) at each visit | The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 to 72 points, with the higher scores reflecting the worse severity of AD | Up to Week 24 | 
| Proportion of patients with Eczema Area and Severity Index (EASI)-90 (≥90 percent reduction in EASI scores from baseline) at each visit | The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 to 72 points, with the higher scores reflecting the worse severity of AD | Up to Week 24 | 
| Change from baseline in Eczema Area and Severity Index (EASI) score at each visit | The EASI score was used to measure the severity and extent of atopic dermatitis (AD) and measures erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 to 72 points, with the higher scores reflecting the worse severity of AD | Up to Week 24 | 
| Proportion of patients with reduction of Pruritus Numerical Rating Scale (NRS) of ≥3 and ≥4 points from baseline | The range of NRS is from 0 (no itch)-10 (worst imaginable itch) | Up to Week 24 | 
| Percent change from baseline in Numerical Rating Scale (NRS) | The range of NRS is from 0 (no itch)-10 (worst imaginable itch) | Up to Week 24 | 
| Body surface area (BSA) of involvement of atopic dermatitis | Change from baseline in percent of BSA | Up to Week 24 | 
| Changes from baseline in Dermatology Life Quality Index (DLQI) at each visit | The DLQI is a 10-item, validated questionnaire used in clinical practice and clinical trials to assess the impact of AD disease symptoms and treatment on quality of life | Up to Week 24 |