Study of MG-K10 Humanized Monoclonal Antibody Injection in Patients With Atopic Dermatitis
Study Details
Study Description
Brief Summary
This study is to reflect the effectiveness and safety of MG-K10 humanized monoclonal antibody injection in patients with moderate to severe atopic dermatitis.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
This study is a multicenter, randomized, double-blind, placebo-controlled phase III study. It is planned to recruit about 498 adult patients with moderate to severe AD who cannot be controlled by local treatment, who will receive multiple subcutaneous injections. The study is divided into screening period (1-5 weeks), double-blind treatment period (16 weeks), treatment maintenance period (36 weeks), and follow-up period (8 weeks)
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: MG-K10 Regimen 1 Every four weeks, subcutaneous injection |
Drug: MG-K10/Placebo
MG-K10 Humanized Monoclonal Antibody Injection
|
| Placebo Comparator: MG-K10 Regimen 2 Every four weeks, subcutaneous injection |
Drug: MG-K10/Placebo
MG-K10 Humanized Monoclonal Antibody Injection
|
Outcome Measures
Primary Outcome Measures
- Proportions of subjects achieving EASI-75 [16 weeks]
Proportions of subjects achieving EASI-75 (≥ 75% decrease from baseline in EASI
- Proportions of subjects achieving IGA score of 0/1 point and a decrease of ≥ 2 [16weeks]
Proportions of subjects achieving IGA score of 0/1 point and a decrease of ≥ 2 points from baseline
Secondary Outcome Measures
- The percentage of subjects who reached EASI-75 at other evaluation points; [16 weeks]
The percentage of subjects who reached EASI-75 at other evaluation points;
- Other evaluation points of view subjects with an IGA score of 0 or 1 [16 weeks]
Other evaluation points of view subjects with an IGA score of 0 or 1 and a decrease of ≥ 2 points from the baseline
- Percentage of subjects who reach EASI-50 [16 weeks]
Percentage of subjects who reach EASI-50 (EASI score is ≥50% lower than the baseline)
- Percentage of subjects who reach EASI-90 [16 weeks]
Percentage of subjects who reach EASI-90 (EASI score is ≥90% lower than the baseline)
- Each evaluation point of view EASI [16 weeks]
Each evaluation point of view EASI score compared with the baseline change and change rate
- Percentage of subjects with a decrease of ≥2 [16 weeks]
Percentage of subjects with a decrease of ≥2 points from the baseline IGA score at each evaluation point of view
- Percentage of subjects with a weekly average of daily peak itching NRS score ≥3 [16 weeks]
Percentage of subjects with a weekly average of daily peak itching NRS score ≥3 points lower than the baseline;
- Percentage of subjects with a weekly average of daily peak itching NRS score ≥4 [16 weeks]
Percentage of subjects with a weekly average of daily peak itching NRS score ≥4points lower than the baseline;
- The weekly average of the daily peak itching NRS [16 weeks]
The weekly average of the daily peak itching NRS score is higher than the baseline change and rate of change;
- The AD of each evaluation visit involves the change and rate of the baseline of BSA; [16 weeks]
The AD of each evaluation visit involves the change and rate of the baseline of BSA;
- The DLQI score of each evaluation interview has changed compared with the baseline. [16 weeks]
The DLQI score of each evaluation interview has changed compared with the baseline.
- The self-evaluation (POEM) score of patients with eczema from each evaluation point of view has changed compared with the baseline; [16 weeks]
The self-evaluation (POEM) score of patients with eczema from each evaluation point of view has changed compared with the baseline;
- The European Five-dimensional Health Scale (EQ-5D) [16 weeks]
The European Five-dimensional Health Scale (EQ-5D) at each evaluation point of view is more than the baseline change and rate of change.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
- age 18-75 years (inclusive of 18 and 75 years), both sexes; 2. patients with AD diagnosed in accordance with the American Academy of Dermatology Consensus Criteria (2014), with a pre-screening diagnosis of AD or history of eczema for ≥1 year, and the following:
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Eczema Area and Severity Index (EASI) score ≥16 at screening and baseline visit;
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Investigator's Overall Assessment (IGA) ≥3 points at screening and baseline visit;
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BSA ≥10% of area of AD involvement at screening and baseline visit
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Weekly mean of peak daily itch NRS score ≥4 at randomization; 3. the patient had an inadequate treatment effect on topical medication or systemic therapy within 6 months prior to the screening visit, or the use of topical medication or systemic therapy was medically inappropriate (e.g., there were important side effects or safety risks);
-
Inadequate therapeutic efficacy was defined as treatment with at least 4 weeks of potent or 2 weeks of ultra-potent topical glucocorticoids (see Appendix) or 4 weeks of topical calcineurin phosphatase inhibitors within the 6 months prior to Screening or, as determined by the Investigator, subjects who had been systemically treated with glucocorticoids or immunosuppressive agents and had failed to achieve or maintain a state of remission from the disease or a state of low disease activity (equivalent to a IGA score of 0 [= clearance] - 2 [= mild]);
-
Significant side effects or safety risks are those that, as assessed by the investigator or the patient's treating physician, outweigh the potential therapeutic benefit, including treatment intolerance, allergic reactions, significant skin atrophy, and systemic reactions; 4. negative screening blood pregnancy test results in women of childbearing age;
-
Females of childbearing age include all females who have had their first menstrual period and are not sterilized (e.g., hysterectomy, tubal ligation on both sides, or bilateral salpingo-oophorectomy) or are not menopausal. Menopausal women were defined as women with ≥12 consecutive months of amenorrhea for no other reason; or women with irregular menstrual cycles undergoing hormone replacement therapy (HRT) with serum follicle-stimulating hormone (FSH) levels >35 mIU/mL; 5. Subjects and partners agree to use effective contraception from the time of signing the informed consent form (ICF) until 6 months after the end of treatment; 6. Voluntarily sign the ICF and be able to comply with the protocol requirements for all visits as well as study-related procedures.
Exclusion Criteria.
Subjects meeting any of the following criteria will not be enrolled in this study:
- subjects with a current diagnosis of other active skin disease (e.g., psoriasis or lupus erythematosus) that may interfere with AD evaluation; 2. known hypersensitivity to any component of the drug; 3. subjects who cannot tolerate venipuncture or have a history of needle or blood sickness; 4. Subjects with co-morbidities that may require systemic hormone therapy or other interventions or require active and frequent monitoring; 5. 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 ≥3 (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 subject or a disease/illness that worsens during the course of the study that would interfere with the validity or safety analyses; 6. Patients with ocular disease that, in the judgment of the Investigator, makes enrollment in the study inappropriate, e.g., past history of atopic keratoconjunctivitis with corneal involvement; if the Investigator is unable to make a determination, a diagnosis will be made by an ophthalmologist; 7. those who plan to undergo major surgery during the study period, including inpatient surgery and daytime outpatient surgery; 8. patients with malignant tumors within 5 years (Note: ① Patients with carcinoma in situ of the cervix who have been resected and have had no evidence of recurrence or metastatic disease for at least 3 years are eligible to participate in this study. ② Patients with basal cell or squamous epithelial carcinoma that has been completely resected and has been free of recurrence for at least 3 years may participate in this study). ; 9.Subjects with the following conditions:
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Persons who have used a biologic agent within 10 weeks prior to randomization or have not exceeded 5 half-lives (whichever is longer);
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Targeted inhibitors (e.g., JAK inhibitors, etc.), systemic glucocorticoids, cyclosporine and other immunosuppressants (e.g., methotrexate, mycophenolate mofetil [MMF], and azathioprine, etc.), phosphodiesterase (PDE4) inhibitors, ultraviolet light therapy, and systemic herbal medicine for AD within 4 weeks prior to randomization;
-
Has received topical glucocorticosteroids, topical calcineurin phosphatase inhibitors, antibiotic compound cream, and topical herbal therapy for AD within 1 week before randomization;
-
Has received allergen-specific immunotherapy within 6 months prior to randomization;
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Live/live attenuated vaccination within 3 months prior to randomization or planned for the duration of the study;
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Participation in a clinical study of another drug in the 3 months or 5 half-lives, whichever is longer, prior to randomization or planning to participate in a clinical study of another drug during the study period;
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Subjects with prior use of an interleukin 4 receptor alpha subunit (IL-4Rα) monoclonal antibody drug who, in the judgment of the investigator, have developed drug resistance or drug-related serious AE;
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Previous participation in the MG-K10 clinical trial; 10. those who have received systemic (oral and intravenous) anti-bacterial, viral, or fungal therapy within 4 weeks prior to randomization; and those who have any current signs, symptoms, or laboratory test abnormalities suggesting the possible presence of acute or subacute infections (e.g., fever, cough, urinary urgency, dysuria, abdominal pain, diarrhea, infected skin wounds, etc.); 11. evidence of active tuberculosis, or previous evidence of active tuberculosis without appropriate documented treatment; chest X-ray (frontal and lateral) or CT, etc. within 3 months prior to/surrounding the screening period suggesting the presence of active tuberculosis infection; 12. confirmed active parasitic infection; suspected parasitic infection or high risk of infection unless active infection has been ruled out by clinical assessment and (if necessary) laboratory assessment prior to randomization; 13. Any one of the following abnormal laboratory test results at screening:
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Absolute neutrophil count (ANC) < 1.2 x 109/L
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Total bilirubin, aspartate aminotransferase (AST), or alanine aminotransferase (ALT) >2 x upper limit of normal (ULN)
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creatinine > 2 x ULN, judged clinically significant by the investigator
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Platelet count <75 x 109/L
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Other laboratory abnormalities of clinical significance, judged by the investigator to be unsuitable for enrollment In the event of any of the above laboratory abnormalities, the test may be repeated within 1 week of obtaining the initial data, and if the measurements obtained from the repeated test meet the criteria for eligibility, they will also be eligible for enrollment; 14. an abnormal 12-lead electrocardiogram (ECG) at screening that, in the opinion of the investigator or sponsor, is clinically significant and may pose an unacceptable risk to the patient's participation in this study (e.g., Fridericia-corrected QT interval >500 msec); 15. Presence of active hepatitis during the Screening Period, or hepatitis B surface antigen (HBsAg) positivity, or hepatitis B core antibody (HBcAb) positivity and hepatitis B virus deoxyribonucleic acid (HBV-DNA) positivity, or hepatitis C virus (HCV) antibody positivity and HCV-ribonucleic acid (HCV-RNA) positivity; 16. Previous history of human immunodeficiency virus (HIV) infection or positive screening HIV antibody; 17. Screening syphilis spirochete antibody positivity; 18. History of drug addiction, substance abuse, or alcoholism (i.e., drinking more than 14 units of alcohol per week (1 unit = 360 mL of beer or 45 mL of 40% alcohol by volume spirits or 150 mL of wine)); 19. women who are breastfeeding or pregnant, or who plan to become pregnant or breastfeed during the study; Persons who, in the opinion of the investigator, have other conditions that make them unsuitable for participation in the study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Huashan Hospital Affiliated to Fudan University | Shanghai | China |
Sponsors and Collaborators
- Shanghai Mabgeek Biotech.Co.Ltd
Investigators
- Principal Investigator: Jianzhong Zhang, Medical Ph.D, Feking University People's Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- MG-K10-AD-003