A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Clinical Study to Evaluate the Efficacy and Safety of SM17 Monoclonal Antibody Injection (Subcutaneous Injection) in Participants With Moderate to Severe Atopic Dermatitis
Overview
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- SinoMab BioScience Ltd
- Enrollment
- 200
- Locations
- 1
- Primary Endpoint
- Efficacy for treating AD - Eczema Area and Severity Index (EASI)
Overview
Brief Summary
This trial is a phase 2, randomized, double-Blind, placebo-Controlled, dose-finding clinical study conducted in participants with moderate-to-severe atopic dermatitis.
The purpose of this study is to evaluate the efficacy, safety, pharmacokinetics , and pharmacodynamics of SM17 (subcutaneous injection) in participants with moderate to severe atopic dermatitis.
Detailed Description
This is a randomized, double-blind, placebo-controlled, parallel-group, dose-finding Phase 2 clinical study of participants with moderate to severe AD to evaluate the efficacy, safety, PK, PD, and immunogenicity of SM17 after multiple SC doses with different dosage regimens. This study will also explore the optimal dosage regimen to provide the basis for dose selection in subsequent clinical studies.
Patients with moderate to severe AD who have an inadequate response to or are intolerant to topical corticosteroids and/or topical calcineurin inhibitors will be enrolled if eligible. The study includes a 4-week screening period, a 16-week double-blind treatment period, a 4-week open-label treatment period, and a safety follow-up period (4 weeks after the last dose).
During the 16-week double-blind treatment period, 200 participants with moderate to severe AD are planned to be enrolled and randomized into 1 of 4 cohorts receiving either SM17 SC or placebo SC.
Participants in each cohort will continue dosing according to the prescribed dosage regimen until Week 14 (until Week 15 for Cohort 4 [QW dosage group]) and will undergo a visit at the end of the double-blind treatment period at Week 16 (Day 113). From Week 16 (Day 113), enrollment to the 4-week open-label treatment period will be at the participant's discretion. Participants who opt to enter the open-label treatment period will be assigned to 1 of 2 cohorts depending on their IGA Score at Week 16.
A safety follow-up will be conducted 4 weeks after the last dose (Week 24). If a participant does not enter the open-label treatment period, safety follow-up will be conducted at 4 weeks after the last dose, and the participant's participation will conclude.
During the study, participants will undergo AD-related clinical efficacy assessments (including investigator assessment and patient-reported scales), safety and tolerability assessments (including laboratory tests), PK, and immunogenicity (ADA) sample collection, and sample collection related to biomarker detection within defined visit windows.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Participants must meet all of the following inclusion criteria to be eligible for study participation:
- •Willing to sign the informed consent form (ICF), comply with the study procedures, and receive follow-up at the time points required in the protocol.
- •Able to understand and complete the study-related questionnaires by themselves or with the assistance of their caregiver/support.
- •Male or female, aged 18 to 70 years (inclusive) at the time of signing the ICF.
- •Meets the diagnostic criteria for AD (as defined by the Hanifin \& Rajka criteria) during the screening period, and had a history of AD or eczema for at least 1 year before the screening.
- •Has an EASI score of ≥16 at screening and baseline.
- •Has an Investigator's Global Assessment (IGA) score of ≥3 (on the basis of the 4 point vIGA-AD scale) at screening and baseline.
- •A body surface area (BSA) of AD involvement ≥10% at screening and baseline.
- •A mean maximum pruritus intensity score of Pruritus Numerical Rating Scale (PP-NRS) ≥4 at baseline.
- •Notes: The baseline pruritus NRS score for maximum pruritus intensity will be determined on the basis of the mean of daily NRS scores for maximum pruritus intensity (score range of 0 to 10) within 7 days before randomization. At least 4 daily scores within 7 days before randomization are required to calculate the baseline mean score. For participants who do not report at least 4 daily scores within 7 days before the scheduled randomization date, randomization should be postponed until this requirement is met, but not exceeding the maximum screening period of 28 days.
Exclusion Criteria
- •Participants who meet any of the following criteria will not be enrolled in the study:
- •Those with general conditions:
- •Female participants who are pregnant (pregnancy is defined as the state from conception until the termination of pregnancy), lactating, or have a positive serum human chorionic gonadotropin test result;
- •Alcohol abuse (ie, an average weekly consumption of \>14 units of alcohol \[1 unit ≈ 360 mL of beer or 45 mL of spirits with 40% alcohol content or 150 mL of wine\]) and/or drug abuse within half a year before screening;
- •Those who experience any of the following in laboratory tests and/or electrocardiogram (ECG) at screening or baseline (if necessary, a repeated test can be conducted for confirmation):
- •Hemoglobin \<100.0 g/L (males), or \<90.0 g/L (females);
- •White blood cell count \<3.0 × 109/L;
- •Neutrophil count \<1.5 × 109/L;
- •Platelet count \<100 × 109/L;
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2 × ULN;
Arms & Interventions
SM17 Group1
participants will receive Dose 1 of SM17 with fixed interval 1 from week 0 to week 15, with a loading dose at Week 0
Intervention: SM17 for subcutaneous injection (Biological)
SM17 Group1
participants will receive Dose 1 of SM17 with fixed interval 1 from week 0 to week 15, with a loading dose at Week 0
Intervention: SM17 placebo for subcutaneous injection (Drug)
SM17 Group2
participants will receive Dose 2 of SM17 with fixed interval 1 from week 0 to week 15，without loading
Intervention: SM17 for subcutaneous injection (Biological)
SM17 Group2
participants will receive Dose 2 of SM17 with fixed interval 1 from week 0 to week 15，without loading
Intervention: SM17 placebo for subcutaneous injection (Drug)
SM17 Group3
participants will receive Dose 3 of SM17 with fixed interval 1 from week 0 to week 15 , with a loading dose at week0
Intervention: SM17 for subcutaneous injection (Biological)
SM17 Group3
participants will receive Dose 3 of SM17 with fixed interval 1 from week 0 to week 15 , with a loading dose at week0
Intervention: SM17 placebo for subcutaneous injection (Drug)
SM17 Group4
participants will receive Dose 3 of SM17 with fixed interval 2 from week 0 to week 15, with a loading dose at Week 0
Intervention: SM17 for subcutaneous injection (Biological)
Open labelled Period
Start from Week 16 , an open-label treatment period will be applied for all participants upon their discretion.
Participants with IGA score 0/1 at week16 will receive Dose 3 of SM17 with Interval 3 until week 20; participants who doesn't reach IGA score 0/1 at week16 will receive Dose 4 of SM17 with Interval 4 until week 20;
Intervention: SM17 for subcutaneous injection (Biological)
Placebo group
Matching placebos for experimental arms 1~4, participants will receive Dose of SM17 placebo with fixed interval 1 or interval 2 (ratio 3:1) from week 0 to week 15 , with a loading dose at Week 0
Intervention: SM17 placebo for subcutaneous injection (Drug)
Outcomes
Primary Outcomes
Efficacy for treating AD - Eczema Area and Severity Index (EASI)
Time Frame: Week 16
To evaluate the efficacy of SM17 in adult participants with moderate to severe atopic dermatitis (AD). Percentage change from baseline (CFB, ≥ -100%, with negatively higher percentage indicating a better response, zero or positive percentage indicating no response or worsening ) in Eczema Area and Severity Index (EASI) at Week 16.
Secondary Outcomes
- Efficacy for treating AD - EASI 50%(Week 12, 16, 24)
- Efficacy for treating AD - EASI 75%(Week 12, 16, 24)
- Efficacy for treating AD - EASI 90%(Week 12, 16, 24)
- Efficacy for treating AD - EASI 100%(Week 12, 16, 24)
- Efficacy for treating AD - IGA 0/1%(Week 12, 16, 24)
- Efficacy for treating AD - PP-NRS(Week 12, 16, 24)
- Efficacy for treating AD-EASI score change(Week 2, 4, 6, 8, 10, 12, 14, 20, 24)
- Efficacy for treating AD- vIGA-AD change(Week 2, 4, 6, 8, 10, 12, 14, 16, 20, 24)
- Efficacy for treating AD - PP-NRS biweekly change(Week 2, 4, 6, 8, 10, 12, 14, 16, 20, 24)
- Efficacy for treating AD - PP-NRS weekly change(Week 1 to 16)
- Efficacy for treating AD - BSA change(Week 2, 4, 6, 8, 10, 12, 16, 20, 24)
- Efficacy for treating AD - SCORAD change(Week 4, 8, 12, 16, 20, 24)
- Efficacy for treating AD - POEM(Week 2, 4, 6, 8, 10, 12, 16, 20, 24)
- Efficacy for treating AD - DLQI(Week 2, 4, 6, 8, 10, 12, 16, 20, 24)
- Incidence of treatment emergent AEs and SAEs(Day0 to Day169)
- Area under the plasma concentration versus time curve (AUC)(Week 0, 1, 2, 4, 8, 12, 14, 15, 16, 20, 24)
- Peak Plasma Concentration (Cmax)(Week 0, 1, 2, 4, 8, 12, 14, 15, 16, 20, 24)
- Time to peak (Tmax)(Week 0, 1, 2, 4, 8, 12, 14, 15, 16, 20, 24)
- Elimination half-life (T1/2)(Week 0, 1, 2, 4, 8, 12, 14, 15, 16, 20, 24)
- Elimination Rate Constant (Kel)(Week 0, 1, 2, 4, 8, 12, 14, 15, 16, 20, 24)
- Total drug clearance from plasma (CL)(Week 0, 1, 2, 4, 8, 12, 14, 15, 16, 20, 24)
- Apparent volume of distribution at steady state after extravascular administration (Vz)(Week 0, 1, 2, 4, 8, 12, 14, 15, 16, 20, 24)
- Immunogenicity(Week 0, 4, 8, 12, 16, 24)