Evaluation of 611 in Chinese Adults With Moderate to Severe Atopic Dermatitis

Study Overview
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Brief Summary
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The primary objective of the study was to evaluate the efficacy and safety of 611 in chinese adults with moderate to severe atopic dermatitis.

Detailed Description
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The maximum study duration was 28 weeks per participants, including a screening period of up to 4 weeks, a 16-week randomized treatment period, and a 8-week follow-up period.

Official Title
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A Multi-Centered, Randomized, Double-Blinded, Placebo-Controlled Phase II Clinical Trial, to Evaluate the Efficacy and Safety of 611 in Chinese Adults With Moderate to Severe Atopic Dermatitis.

Conditions
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Dermatitis, Atopic

Intervention / Treatment
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* Drug: 611 Q2W
* Drug: 611 Q4W
* Drug: Matching placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must be able to understand and comply with the requirements of the study. and must participate voluntarily and sign the written informed consent. Male or female adults ages 18 to 64 years old when signing the informed consent. AD (according to American Academy of Dermatology Consensus Criteria, 2014) that had been present for at least 1 years before the screening visit. Eczema Area and Severity Index (EASI) score greater than or equal to (>=) 16 at the screening and baseline visits. Investigator's Global Assessment (IGA) score >=3 (on the 0 to 4 IGA scale, in which 3 was moderate and 4 was severe) at the screening and baseline visits. Participants with >=10 percent (%) body surface area (BSA) of AD involvement at the screening and baseline visits. Baseline Pruritus Numerical Rating Scale (NRS) average score for maximum itch intensity >=4. Recent history (within 12 months before the screening visit) of inadequate response to treatment with topical medications or for whom topical treatments were otherwise medically inadvisable (e.g., because of important side effects or safety risks). Have applied a stable dose of topical emollient (moisturizer) twice daily for at least the 7 consecutive days immediately before the baseline visit. Female subjects of reproductive age (and their male partners) and male subjects (and their female partners) must use highly effective contraception throughout the study period and for at least 3 months after the last dose. The subjects had no plans to pregnancy, donate sperm or donate egg during the whole study period and for at least 3 months after the last dose. Exclusion Criteria: Presence of skin comorbidities that may interfere with study assessments Presence of active endoparasitic infections; or suspected endoparasitic. Any history of vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC). History of malignancy within 5 years before the baseline visit, except completely treated in situ carcinoma of the cervix at least 1 year, completely treated and resolved non-metastatic squamous or basal cell carcinoma of the skin at least 1 year. Active chronic or acute infection requiring treatment with systemic anti-infective therapy within 2 weeks before the baseline visit, or superficial skin infections within 1 week before the baseline visit. Known or suspected history of immunosuppression, including history of invasive opportunistic infections (e.g., histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis) despite infection resolution: or unusually frequent infections, per investigator judgment. Active TB, unless that was well documented that the participants had adequately treated. Any medical condition that, in the opinion of the investigator, is serious or unstable and may affect the subject's safety and/or prevent the subject from completing the study Patients who have received any of the following treatments: a) Treatment with topical drugs such as corticosteroids, topical calcineurin inhibitors, PDE inhibitors, or Janus kinase (JAK) inhibitors within 2 weeks before baseline; b) Treatment with systemic traditional Chinese medicine (TCM) within 4 weeks before baseline or treatment with topical TCM; c) Have undergone bleaching baths ≥ twice within 2 weeks before baseline; d) Treatment with systemic corticosteroids or other immunosuppressive/immunomodulating substances (e.g., cyclosporine, mycophenolate mofetil, azathioprine, methotrexate, interferon-gamma [IFN-γ], oral JAK inhibitors, compound glycyrrhizin, azathioprine, mycophenolate mofetil, or methotrexate,) within 4 weeks before baseline or 5 drug half-lives (if known), whichever is longer; e) Treatment with phototherapy (narrow band ultraviolet B [NBUVB], ultraviolet B [UVB], ultraviolet A1 [UVA1], psoralen + ultraviolet A [PUVA]), sunbed or any other light emitting device (LED) therapy within 4 weeks before baseline; f) Treatment with cell depletion agents (e.g., rituximab) within 6 months before baseline. Treatment with other biological agents (e.g., dupilumab) within 3 months before baseline or 5 drug half-lives (if known), whichever is longer; g) History of inadequate response to treatment with anti-IL-4 and/or IL13 agents (e.g., dupilumab), in the opinion of the investigator. h) Treatment with allergen specific immunotherapy (SIT) within 6 months before the screening visit. i) Initiation of treatment of AD with prescription moisturizers or moisturizers containing additives such as ceramide, hyaluronic acid, urea, or filaggrin degradation products during the screening period (participants may continue using stable doses of such moisturizers if initiated before the screening visit). Presence of any one of the following lab abnormalities at screening or baseline: a) Total bilirubin > 1.5 times the upper limit of normal (ULN); b) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 ULN; c) Serum creatinine (Cr) > 1.5×ULN; d) White blood cell count below the lower limit of normal (LLN) , was judged clinically significant by the investigator, and not suitable for inclusion in the study; HBsAg-positive with HBV DNA copy number beyond normal limit of the HBV DNA test, or HCV antibodies (HCV Ab)-positive with HCV RNA copy number beyond normal limit of the HCV RNA test, human immunodeficiency virus antibody (HIV Ab) positive, serum syphilis helix antibody (TP Ab) positive with syphilis helix titrating positive at screening; History of alcohol or drug abuse within 6 months before baseline. History of hypersensitivity to 611 or their excipients. Have been vaccinated with live (attenuated) vaccine within 2 months before baseline or planned during the study period; Have used any investigational drug/treatment within 8 weeks before baseline; Planned or anticipated major surgical procedure during the patient's participation in this study. Pregnant or lactating women, or subjects with pregnancy or lactation plans during the study period. Any reason which, in the opinion of investigator, would prevent the subject from participating in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 611 Q2W<br>Four subcutaneous injections of 611 150 mg (for a total of 600 mg) as a loading dose on Week 0 Day 1, followed by two 150 mg injections (for a total of 300 mg) q2w from Week 2 to Week 14 (7 cycles). | Drug: 611 Q2W<br>* subcutaneous injection, 600mg (loading dose, week 0) + 300mg Q2W (maintenance dose, from Week 2 to Week 14, 7 cycles)<br>|
| Experimental: 611 Q4W<br>Four subcutaneous injections of 611 150 mg (for a total of 600 mg) as a loading dose on week 0 Day 1, followed by two 150 mg injections (for a total of 300 mg) q4w on week 4, 8, 12 and two injections of placebo on week 2, 6, 10, 14. | Drug: 611 Q4W<br>* subcutaneous injection, 600mg (loading dose, Day1) + 300mg Q4W (maintenance dose, on week 4, 8, 12) + placebo Q4W (on week 2, 6, 10, 14)<br>|
| Placebo Comparator: placebo<br>Four subcutaneous injections of placebo as a loading dose on week 0 Day 1, followed by two injections q2w from Week 2 to Week 14 (7 cycles). | Drug: Matching placebo<br>* subcutaneous injection, Q2W, from Week 2 to Week 14, 7 cycles<br>* Other names: placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Eczema Area and Severity Index (EASI) - 75 Response (>= 75% Improvement in Score From Baseline) at Week 16 | 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 range from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. | Baseline, Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With EASI-50 (>=50% Improvement From Baseline) at Week 16 | 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 range from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. | Baseline, Week 16 | 
| Number of Participants With EASI-90 (>=90% Improvement From Baseline) at Week 16 | 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 range from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. | Baseline, Week 16 | 
| Number of Participants With Investigator's Global Assessment (IGA) Score of 0 or 1 and Improvement From Baseline of Greater Than or Equal to (>=) 2 Points From Baseline to Week 16 | The IGA is an assessment instrument used to rate the severity of AD globally based on a 5-point scale ranging from (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe), higher score indicated higher severity. | Baseline to Week 16 | 
| Number of Participants Who Achieve Improvement of IGA Score by >=2 From Baseline to Week 16 | The IGA is an assessment instrument used to rate the severity of AD globally based on a 5-point scale ranging from (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe), higher score indicated higher severity. | Baseline to Week 16 | 
| Number of Participants Who Achieved >=4 Points With Improvement From Baseline in Weekly Average of Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16 | Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 [0 = no itch; 10 = worst itch imaginable]), higher scores indicated greater severity. | Baseline to Week 16 | 
| Number of Participants Who Achieved >=3 Points With Improvement From Baseline in Weekly Average of Pruritus Numerical Rating Scale (NRS) Score From Baseline to Week 16 | Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 [0 = no itch; 10 = worst itch imaginable]), higher scores indicated greater severity. | Baseline to Week 16 | 
| Percentage Change From Baseline to Week 16 in EASI Score | 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 range from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD. | Baseline to Week 16 | 
| Change From Baseline to Week 16 in Percent Body Surface Area (BSA) of AD Involvement | BSA affected by AD was assessed for each section of the body (the possible highest score for each region was: head and neck [9%], anterior trunk [18%], back [18%], upper limbs [18%], lower limbs [36%], and genitals [1%]) and reported as a percentage of all major body sections combined. The reported percentage of BSA was combined percentage of all major body sections. | Baseline to Week 16 | 
| Change From Baseline at Week 16 in Weekly Average of Pruritus NRS | Pruritus NRS was an assessment tool that was used to report the intensity of a participant's pruritus (itch), during a 24-hour recall period. Participants were asked the following question: how would a participant rate his itch at the worst moment during the previous 24 hours (for maximum itch intensity on a scale of 0 - 10 [0 = no itch; 10 = worst itch imaginable]), higher scores indicated greater severity. | Baseline to Week 16 | 
| Change From Baseline to Week 16 in Dermatology Life Quality Index (DLQI) Total Score | The DLQI was a validated questionnaire used to measure the impact of AD disease symptoms and treatment on health-related quality of life (QOL). DLQI consisting of a set of 10 questions which assess QOL over the past week. Responses to each questions were assessed on a scale of 0 to 3, where 0 is not at all and 3 is very much. Scores from all 10 questions added up to give total DLQI scores ranged from 0 (not at all) to 30 (very much), higher scores indicated more impact on quality of life. | Baseline to Week 16 | 
| Change From Baseline to Week 16 in Patient Oriented Eczema Measure (POEM) | The POEM is a 7-item self-assessment questionnaire that assesses disease symptoms on a scale ranging from 0 to 4 (0 = no days, 1 = 1 to 2 days, 2 = 3 to 4 days, 3 = 5 to 6 days, 4 = all days). The sum of the 7 items gives the total POEM score of 0 (absent disease) to 28 (severe disease). Higher scores indicated more severe disease and poor quality of life. | Baseline to Week 16 | 
| Adverse events (AEs), measurement of vital signs，physical examination，electrocardiogram and laboratory tests at each visit. | The incidence and severity of treatment emergent adverse event (TEAE), including Serious Adverse Event (SAE), as well as clinical symptoms, and any abnormalities of vital signs, physical examinations，electrocardiogram，laboratory tests and, etc. | Up to 24 Weeks | 
| Maximum Concentration (Cmax). | Maximum Observed Serum Concentration (Cmax) of 611 | Baseline to Week 24. | 
| Minimum concentration (Cmin). | Minimum concentration (Cmin) of 611. | Baseline to Week 24. | 
| Time to Reach the Maximum Concentration (Tmax). | Time to Reach the Maximum Serum Concentration (Tmax) of 611. | Baseline to Week 24. | 
| Area under the serum concentration-time curve from 0 to the time of the last quantifiable concentration (AUC0-last). | Area under the serum concentration-time curve from 0 to the time of the last quantifiable concentration (AUC0-last) of 611. | Baseline to Week 24. | 
| AUC to the end of the dosing period (AUC0-tau) | AUC to the end of the dosing period (AUC0-tau) of 611. | Baseline to Week 24. | 
| Clearance rate (CL/F). | Clearance rate (CL/F) of 611. | Baseline to Week 24. | 
| Percentage of Participants With Anti-drug Antibodies and Neutralizing Antibodies. | Immunogenicity assessment will be based on Anti-drug Antibodies (ADAs) response and development of Neutralizing Antibodies (NABs). Percentage is calculated based on the number of evaluable participants and was calculated by number of participants with treatment-emergent positive anti-drug antibodies / number of evaluable participants * 100%. | Baseline to Week 24. | 
| Change in serum concentrations of Thymus and activation regulated chemokine (TARC) | Change in serum concentrations of TARC | Baseline to Week 24. | 
| Change in serum concentrations of IL-4 | Change in serum concentrations of IL-4 | Baseline to Week 24. | 
| Change in serum concentrations of IL-13 | Change in serum concentrations of IL-13. | Baseline to Week 24. | 
| Change in serum concentrations of IgE | Change in serum concentrations of IgE. | Baseline to Week 24. | 
| Change in whole blood eosinophil counts | Change in whole blood eosinophil counts. | Baseline to Week 24. | 
| Change in serum concentrations of lactate dehydrogenase (LDH) | Change in serum concentrations of lactate dehydrogenase (LDH). | Baseline to Week 24. |