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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Moderate-to-severe Atopic Dermatitis
• Intervention / Treatment: Other: Placebo; Biological: CM326

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 54
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Qian Jia; Phone Number: +862888610620; Email: qianjia@keymedbio.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Recruiting
      • Peking University People's Hospital
      • Contact: Jianzhong Zhang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CM326 55 mg, once every two weeks (Q2W); 55mg for 6 doses, every 2 weeks, subcutaneous (SC)	Biological: CM326; CM326 injection
Experimental: CM326 110 mg, once every two weeks (Q2W); 110mg for 6 doses, every 2 weeks, subcutaneous (SC)	Biological: CM326; CM326 injection
Experimental: CM326 110 mg, once every four weeks (Q4W); 110mg for 3 doses, every 4 weeks, subcutaneous (SC)	Biological: CM326; CM326 injection
Experimental: CM326 220 mg, once every two weeks (Q2W); 220mg for 6 doses, every 2 weeks, subcutaneous (SC)	Biological: CM326; CM326 injection
Experimental: CM326 220 mg, once every four weeks (Q4W); 220mg for 3 doses, every 4 weeks, subcutaneous (SC)	Biological: CM326; CM326 injection
Placebo Comparator: Placebo; Placebo for 6 doses, every 2 weeks, subcutaneous (SC) and placebo for 3 doses, every 4 weeks, subcutaneous (SC)	Other: Placebo; Placebo

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Keymed Biosciences Co.Ltd

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2022
• Primary Completion (Anticipated): January 1, 2023
• Study Completion (Anticipated): January 1, 2023

Study Registration Dates

• First Submitted: December 13, 2021
• First Submitted That Met QC Criteria: December 23, 2021
• First Posted (Actual): January 11, 2022

Study Record Updates

• Last Update Posted (Actual): March 9, 2022
• Last Update Submitted That Met QC Criteria: February 21, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Eczema; Dermatitis, Atopic
• Other Study ID Numbers: CM326AD001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No