A Clinical Study to Evaluate SM17 for Atopic Dermatitis

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

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.

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.

Inclusion Criteria:

Participants must meet all of the following inclusion criteria to be eligible for study participation:

1. 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.

2. Able to understand and complete the study-related questionnaires by themselves or with the assistance of their caregiver/support.

3. Male or female, aged 18 to 70 years (inclusive) at the time of signing the ICF.

4. 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.

5. Has an EASI score of ≥16 at screening and baseline.

6. Has an Investigator's Global Assessment (IGA) score of ≥3 (on the basis of the 4 point vIGA-AD scale) at screening and baseline.

7. A body surface area (BSA) of AD involvement ≥10% at screening and baseline.

8. 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.

9. Participants with a recent (within 6 months before the screening visit) medical history indicating that they have an inadequate response to topical medications or that the use of topical medications is medically inappropriate (eg, with important side effects or safety risks);

   1. Notes: Inadequate response is defined as failure to achieve or maintain disease remission or low disease activity (equivalent to IGA score of 0 [= none] to 2 [= mild]) even on a daily treatment regimen of moderate-to-strong topical corticosteroids (TCSs) (±topical calcineurin inhibitors [TCIs], if applicable) for at least 28 days or up to the maximum recommended course of treatment in the product prescription information (eg, 14 days for ultra-strong TCSs), whichever is shorter.
   2. Important side effects or safety risks are those that, as assessed by the investigator or the participant's attending physician, outweigh the potential benefit of treatment, including treatment intolerance, allergic reactions, significant skin atrophy, and systemic reactions.

10. Those who use topical mild emollients (moisturizers) at least twice daily for at least 7 consecutive days before randomization. For restrictions on the types of emollients not allowed during the study, see exclusion criterion 5.

11. Eligible participants of childbearing potential and their partners must agree to use a medically accepted contraceptive measure (eg, intra-uterine contraceptive device, anticonceptive or condom, or abstinence) during the study and for 6 months after the end of the study, with specific contraceptive measures detailed in the protocol; and have no plans to donate sperm/ova during the study and within 6 months after the end of the study.

Exclusion Criteria:

Participants who meet any of the following criteria will not be enrolled in the study:

1. Those with general conditions:

   1. 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;
   2. 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;

2. 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):

   1. Hemoglobin <100.0 g/L (males), or <90.0 g/L (females);
   2. White blood cell count <3.0 × 109/L;
   3. Neutrophil count <1.5 × 109/L;
   4. Platelet count <100 × 109/L;
   5. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 × ULN;
   6. Bilirubin total (T-BIL) >1.5 × ULN;
   7. Serum creatinine >1.5 × ULN;
   8. A positive hepatitis B surface antigen (HBsAg) test result, a positive hepatitis B core antibody (HbcAb) test result with HBV DNA level above the upper limit of the normal range, or the HIV and anti-hepatitis C virus (HCV) antibody test results are positive with positive HCV RNA, or syphilis infection is present (when the syphilis specific antibody test result is positive, the non-specific antibody test for syphilis shall be added for validation).
   9. ECG at screening indicates clinically significant abnormalities that may affect the safety of participants, including but not limited to acute myocardial ischemia, myocardial infarction, serious arrhythmia or significant QTcF prolongation (QT interval corrected by Fridericia's formula, QTcF ≥450 ms for males and ≥470 ms for females);

3. Those with any of the following medical history or comorbidities:

   1. History of vernal keratoconjunctivitis (VKC) and/or atopic keratoconjunctivitis (AKC); or active dermatosis that may confound the diagnosis of AD or interfere with the evaluation of treatment (eg, psoriasis, body tinea, cutaneous lupus erythematosus), generalized pigmentation or extensive scarring, or other types of eczema (allergic contact dermatitis);
   2. Known or suspected history of immunosuppressive diseases, including history of invasive opportunistic infections (eg, tuberculosis, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, or aspergillosis), although having been relieved; or abnormally frequent, recurrent or long-term infections as judged by the investigator;
   3. Participants with chronic active or acute infections requiring systemic treatment with antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks before screening or from screening to baseline;
   4. Those with current evidence of active tuberculosis (TB) or occult TB infections (abnormal chest CT results determined by research show the presence of active TB, and suspected latent or old TB lesions can be confirmed by QuantiFERON Gold test at the discretion of the investigator);
   5. Those definitively diagnosed with lymphoma, leukemia, or any malignant tumor within 5 years before screening (except squamous cell carcinoma of skin, basal cell carcinoma, or carcinoma cervix in situ that is completely resected without evidence of recurrence);
   6. Previous or current significant medical diseases that will interfere with the study process and/or evaluation, as considered by the investigator, including but not limited to cardio-cerebrovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, nervous system and psychiatric diseases, as well as other conditions that are inappropriate for participation in the study, as judged by the investigator;
   7. The participant has a history of allergy to SM17 or its components, or a history of immediate allergy to other drugs (as defined by Sampson criteria), a history of allergy to monoclonal antibodies and their components, clinically significant multiple or severe drug allergies, or severe post-treatment hypersensitivity (including but not limited to severe erythema multiforme, toxic epidermal necrolysis or Stevens-Johnson syndrome, and dermatitis exfoliative); Notes: Sampson criteria: 1.) Acute onset of an illness with involvement of the skin, mucosal tissue or both, and at least one of respiratory compromises, reduced blood pressure (BP) or associated symptoms of end-organ dysfunction; 2.) Any 2 or more of the above symptoms that occur rapidly after exposure to a likely allergen for that patient; 3.) Reduced BP after exposure to known allergen for that participant.

4. Those who use any of the following medications/treatments and are not expected to withdraw/discontinue such treatment(s) throughout the study:

   1. Systemic application of corticosteroids, immunosuppressants, Janus kinase inhibitors for AD within 4 weeks before baseline;
   2. Antihistamines or inhaled corticosteroids within 1 week before baseline (those who have been treated with antihistamines or inhaled corticosteroids at a stable dose for at least 7 days before baseline and are scheduled to continue to use them during the study may be enrolled);
   3. Systemic herbal therapy for AD within 4 weeks before baseline;
   4. Ultraviolet therapies for AD (including but not limited to narrow-band ultraviolet B [NB-UVB] or medium-to high-dose UVA1) or regular use of artificial sunbathing for AD within 4 weeks before baseline;
   5. ≥2 bleach baths within 2 weeks before baseline;
   6. The following topical medications for the treatment of AD within 1 week before baseline: a) Topical corticosteroids or topical calcineurin inhibitors; b) Other alternative therapy including topical traditional Chinese medicines; c) Other topical medications (including but not limited to topical phosphodiesterase-4 [PDE-4] inhibitors);
   7. Those who have received biologics for AD before baseline: a) Any cell scavenger and/or cell depleting agent, including but not limited to rituximab; b) Other biologics: within 5 half-lives (if known) or 16 weeks before baseline, whichever is longer;
   8. Those who have received allergen-specific immunotherapies within 6 months before baseline;

5. Those who have used prescription emollients or emollients containing active ingredients (eg, ceramides, hyaluronic acid, urea, or filaggrin degradation products) within 1 week before baseline;

6. Those who have undergone major surgery within 3 months before baseline or who have not yet recovered after the surgery, or who plan to undergo major surgery during the study;

7. Those who have a history of blood donation or severe blood loss (total blood volume ≥500 mL) within 1 month before screening, or have received transfusion within 2 months before screening; or who have donated bone marrow stem cells within 3 months before screening;

8. Those who have received an attenuate live vaccine within 3 months before baseline, or plan to receive an attenuated live vaccine during the study;

9. Those who have participated in other interventional clinical studies (have signed an ICF and received active drug/device treatment) within 6 months before baseline;

10. Those who have participated in an anti-IL-25 antibody, or anti-IL-17RB antibody (including SM17) clinical study; Those who have had other conditions within 12 months before screening that, in the opinion of the investigator, may pose a risk to the participants' participation in this study or may interfere with study procedures