Moderate-to-severe Atopic Dermatitis
Conditions
Brief summary
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
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.
Interventions
BIOLOGICALCM326
CM326 injection
OTHERPlacebo
Placebo
Sponsors
Keymed Biosciences Co.Ltd
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events (AE) | Up to week 24 | Incidence of AEs, including any abnormal physical examinations, abnormal vital signs, abnormal ECG, and abnormal lab testing. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK) parameter : Peak Plasma concentration (Cmax) | Up to Week 24 | Peak Plasma concentration (Cmax) |
| Pharmacokinetics (PK) parameter : Area under the plasma concentration-time curve (AUC) | Up to Week 24 | Area under the plasma concentration-time curve (AUC) |
| Pharmacokinetics (PK) parameter : Clearance rate (CL/F) | Up to Week 24 | Clearance rate (CL/F) |
| Pharmacokinetics (PK) parameter : Elimination half life (T1/2z) | Up to Week 24 | Elimination half life (T1/2z) |
| Proportion of patients with Investigator's Global Assessment (IGA) score = 0-1 at each visit | Up to Week 24 | IGA is a 6-point scale ranging from 0 (clear) to 5 (very severe) |
| Pharmacodynamics (PD): Changes from baseline in serum thymus activation regulation chemokine (TARC) concentration after CM326 administration | Up to Week 24 | Changes from baseline in serum thymus activation regulation chemokine (TARC) concentration after CM326 administration |
| Pharmacodynamics (PD): Changes from baseline in eosinophil count after CM326 administration | Up to Week 24 | Changes from baseline in eosinophil count after CM326 administration |
| Pharmacodynamics (PD): Changes from baseline in serum total immunoglobulin E (IgE) concentration after CM326 administration | Up to Week 24 | Changes from baseline in serum total immunoglobulin E (IgE) concentration after CM326 administration |
| Pharmacodynamics (PD): Changes from baseline in plasma interleukin-5 (IL-5) concentration after CM326 administration | Up to Week 24 | Changes from baseline in plasma interleukin-5 (IL-5) concentration after CM326 administration |
| Pharmacodynamics (PD): Changes from baseline in plasma interleukin-13 (IL-13) concentration after CM326 administration | Up to Week 24 | Changes from baseline in plasma interleukin-13 (IL-13) concentration after CM326 administration |
| Pharmacokinetics (PK) parameter: Time to reach peak concentration (Tmax) | Up to Week 24 | Time to reach peak concentration (Tmax) |
| Immunogenicity: anti-drug antibody (ADA) and neutralizing antibody (Nab) | Up to Week 24 | Detection of anti-drug antibody (ADA) and neutralizing antibody (Nab) |
| Proportion of patients with IGA reduction from baseline of ≥2 points at each visit | Up to Week 24 | IGA is a 6-point scale ranging from 0 (clear) to 5 (very severe) |
| Proportion of patients with Eczema Area and Severity Index (EASI)-50 (≥50 percent reduction in EASI scores from baseline) at each visit | Up to Week 24 | 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 |
| Proportion of patients with Eczema Area and Severity Index (EASI)-75 (≥75 percent reduction in EASI scores from baseline) at each visit | Up to Week 24 | 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 |
| Proportion of patients with Eczema Area and Severity Index (EASI)-90 (≥90 percent reduction in EASI scores from baseline) at each visit | Up to Week 24 | 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 |
| Change from baseline in Eczema Area and Severity Index (EASI) score at each visit | Up to Week 24 | 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 |
| Proportion of patients with reduction of Pruritus Numerical Rating Scale (NRS) of ≥3 and ≥4 points from baseline | Up to Week 24 | The range of NRS is from 0 (no itch)-10 (worst imaginable itch) |
| Percent change from baseline in Numerical Rating Scale (NRS) | Up to Week 24 | The range of NRS is from 0 (no itch)-10 (worst imaginable itch) |
| Body surface area (BSA) of involvement of atopic dermatitis | Up to Week 24 | Change from baseline in percent of BSA |
| Changes from baseline in Dermatology Life Quality Index (DLQI) at each visit | Up to Week 24 | 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 |
| Pharmacodynamics (PD): Changes from baseline in serum periostin concentration after CM326 administration | Up to Week 24 | Changes from baseline in serum periostin concentration after CM326 administration |
Countries
China
Contacts
Primary ContactQian Jia
Outcome results
None listed