A Randomized, Double-Blind, Placebo-Controlled Phase III Clinical Study of MG-K10 Humanized Monoclonal Antibody Injection in Adult and Adolescent Patients with Moderate-to-Severe Atopic Dermatitis

Prior treatment

• Participants with any of the following conditions: − Use of biologics (e.g., IL-31 [Nemolizumab]), within 10 weeks prior to randomization or within 5 half-lives (whichever is longer). − Use of targeted inhibitors (e.g., JAK inhibitors), systemic corticosteroids, cyclosporine, or other immunosuppressants (e.g., methotrexate, mycophenolate mofetil [MMF], azathioprine), phosphodiesterase 4 (PDE4) inhibitors, ultraviolet therapy, or systemic herbal medicine for AD within 4 weeks prior to randomization. − Use of topical treatments for AD such as topical corticosteroids, topical calcineurin inhibitors, antibiotic compound creams, or topical herbal medicine within 1 week prior to randomization. − Receipt of allergen-specific immunotherapy within 6 months prior to randomization. − Vaccination with live or attenuated live vaccines within 3 months prior to randomization or planned during the study period. − Participation in another clinical drug study within 3 months or 5 half-lives (whichever is longer) prior to randomization or plans to participate in another clinical drug study during the study period. − Previous use of interleukin-4 receptor alpha (IL-4Rα) or interleukin-13 (IL-13) monoclonal antibody drugs (Include but not limited to dupilumab, tralokinumab, or lebrikizumab) with investigator-assessed resistance or serious adverse events (AEs) related to the drug. − Previous participation in an MG-K10 clinical trial.
• Evidence of active tuberculosis (TB); history of prior active TB without documented adequate anti-TB treatment; or chest X-ray or chest CT obtained within 3 months prior to screening suggestive of active TB. For participants without the above conditions, TB screening must include a chest radiograph (frontal and lateral) or chest CT; chest radiograph is preferred. Study sites may alternatively perform interferon-gamma release assay (IGRA) or tuberculin skin test (TST) or other comparable tests for TB screening in accordance with local clinical practice. If IGRA or TST is positive, further imaging evaluations shall be conducted to determine active TB
• Known allergies to any component of the investigational drug.
• The participant has comorbidities that may require systemic steroid therapy, other intervention measures, or require active and frequent monitoring.
• Participants are planning to undergo major surgery during the study period, including inpatient and outpatient surgeries.

Other illness

• Active hepatitis at screening, or positive for hepatitis B surface antigen (HBsAg), or positive for hepatitis B core antibody (HBcAb) with hepatitis B virus DNA (HBV-DNA) positive, or positive for hepatitis C virus (HCV) antibodies with HCV RNA positive
• History of human immunodeficiency virus (HIV) infection, or positive for HIV antibodies at screening.
• History of alcohol or drug abuse within 2 years before the screening visit (i.e., weekly consumption exceeding 14 units of alcohol, where 1 unit = 360 mL beer, 45 mL spirits at 40% alcohol, or 150 mL wine).
• The participant currently has a diagnosis of another active skin disease that may affect AD evaluation (e.g., psoriasis or lupus erythematosus).
• Any other conditions that the investigator considers inappropriate for study participation.
• The participant cannot tolerate venipuncture or have a history of needle or blood phobia.
• Participants with ocular diseases deemed unsuitable for study entry by the investigator, such as a history of atopic keratoconjunctivitis involving the cornea. If the investigator cannot decide, an ophthalmologist’s diagnosis is required.
• Patients with malignant tumors within 5 years (Note: 1. Patients with in-situ cervix cancer that has been resected and have no evidence of recurrence or metastatic lesions for at least 3 years are eligible for this study. 2. Patients with basal cell or squamous epithelial carcinoma that has been completely resected and has not recurred for at least 3 years may participate in this study.).

Lab values

• Received systemic (oral or intravenous) antibacterial, antiviral, or antifungal treatment within 4 weeks prior to randomization. Currently exhibits any symptoms, signs, or laboratory abnormalities suggesting possible acute or subacute infections (e.g., fever, cough, urinary urgency, dysuria, abdominal pain, diarrhea, infected skin wounds).
• Diagnosis of active parasitic infection; suspected parasitic infection or high risk of infection unless clinical and (if necessary) laboratory evaluations have ruled out active infection prior to randomization.
• Laboratory results at screening showing any of the following abnormalities: 1) Absolute neutrophil count (ANC) < 1.2×109/L. 2) Total bilirubin, aspartate aminotransferase (AST), or alanine aminotransferase (ALT) > 2 times the upper limit of normal (ULN). 3) Creatinine > 2× ULN, deemed clinically significant by the investigator. 4) Platelet count < 75×109/L. 5) Other clinically significant laboratory abnormalities, as determined by the investigator, rendering the participant unsuitable for inclusion. In cases where any of the above-mentioned laboratory abnormalities are present, a retest may be performed within 1 week of obtaining the initial data. If the values from the retest meet the eligibility criteria, the participant may qualify for inclusion
• Abnormal 12-lead electrocardiogram (ECG) at screening, which the investigator considers clinically significant and possibly posing an unacceptable risk for the participant in this study (e.g., Fridericia-corrected QT interval > 500 msec).
• Positive for Treponema pallidum antibodies (TP-Ab) at screening, except if rapid plasma reagin (RPR) or Toluidine Red Unheated Serum Test (TRUST) results are negative.
• Those with significant cardiac, pulmonary, gastrointestinal, hepatic, renal, hematologic, neurologic, and psychiatric disorders that are unstable or not well controlled and are considered clinically significant by the investigator. For example, patients with expected survival shorter than 3 months, patients with uncontrolled diabetes mellitus (glycated hemoglobin [HbA1c] ≥9%), patients with cardiovascular disease [e.g., cardiac function ≥class III (NYHA classification)], severe renal disease (e.g., patients on dialysis), hepatobiliary disease (e.g., Child-Pugh class B or C), neurologic disease (e.g., demyelinating disease), active autoimmune diseases (e.g., lupus erythematosus, inflammatory bowel disease, and rheumatoid arthritis). "Clinically significant" is defined as participation in a study that, in the opinion of the investigator, poses a risk to the safety of the participant or would compromise the validity or safety analysis in the event of an exacerbation of the disease/illness during the study.

Other

• Participants who meet any of the following criteria will be excluded from this study: 1.Body weight < 30 kilograms (kg).
• Women who are breastfeeding, pregnant, or planning to become pregnant or breastfeed during the study period.

• Participants meeting all the following criteria are eligible for this study: Age: ≥12 years, both males and females. Country-specific requirement: In the Czech Republic, participants must be aged ≥18 years
• Diagnosed with AD (according to the 2014 American Academy of Dermatology Consensus Criteria) that has been present for ≥1 year before the screening visit, and meeting the following conditions: − Eczema Area and Severity Index (EASI) score ≥ 16 at both screening and baseline visits. − Investigator’s Global Assessment (IGA) score ≥ 3 at both screening and baseline visits. − Body Surface Area (BSA) affected by AD ≥ 10% at both screening and baseline visits. − Weekly average of daily peak pruritus NRS score ≥ 4 at randomization.
• Within 6 months prior to the screening visit, the patient has shown an insufficient response to topical medication or is medically unsuitable for topical treatment (e.g., significant side effects or safety risks). − Definition of Insufficient Response: Lack of achievement or maintenance of disease remission or low disease activity status (IGA score of 0 [no symptoms] to 2 [mild symptoms]) despite treatment with potent topical corticosteroids for at least 4 weeks, ultra-potent corticosteroids for at least 2 weeks, or topical calcineurin inhibitors for at least 4 weeks within the 6 months prior to screening. If the investigator determines that the participant has previously used systemic corticosteroids or immunosuppressants but has not achieved or maintained disease remission or low disease activity status (IGA score of 0 [no symptoms] to 2 [mild symptoms]), this is also considered an insufficient response to topical treatments. − Significant side effects or safety risks are defined as adverse effects or risks, as assessed by the investigator or the patient’s primary care physician, that outweigh the potential therapeutic benefits. This includes treatment intolerance, allergic reactions, significant skin atrophy, and systemic reactions.NOTE: Participants must, in the investigator's judgment, be able to safely discontinue any prohibited systemic treatment for AD and complete the protocol-defined washout period prior to randomization, without posing an unacceptable risk to the participant.
• Participants should start a stable dose of moisturizer from the signing of ICF, apply a moisturizer twice daily for at least 7 consecutive days prior to randomization and continue using it throughout the study period
• Women of childbearing age have a negative blood pregnancy test result during the screening period. A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy (see Appendix 9).
• Participants and their partners agree to use effective contraception from the time of signing the Informed Consent Form (ICF) until 6 months after the last administration of study treatmen(see Appendix 9 for details of effective contraception); no donation or freezing of germ cells is allowed from the time of signing the ICF until 6 months after the last administration of study treatment
• The participant voluntarily signs the ICF and can comply with all required visits and study-related procedures outlined in the protocol.
• For participants ≥ 12 and < 18 years of age at Screening Visit: Parent or legal guardian, as required, has voluntarily signed and dated an informed consent form, approved by an IEC, after the nature of the study has been explained and the participant's parent or legal guardian has had the opportunity to ask questions. Participants will be included in all discussions to obtain verbal/and or written assent. Parent/legal guardian and participant must comply with the requirements of this study protocol. If a participant becomes of legal age during the study, that participant will need to be consented using the approved informed consent form.