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1.ASLAN004 MOA -¼v¤ù
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www.dupixenthcp.com/atopicdermatitis/about/mechanism-of-action

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MOA
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www.dupixenthcp.com/atopicdermatitis/about/mechanism-of-action


MOA
www.tsim.org.tw/journal/jour29-6/02.PDF?fbclid=IwAR2B85aLqBUAt5agx6K7u0NkCGTGpr7w6HDCagHhLuu54ZH7FEqHMAdXG3M

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Lebrikizumab ¤T´Á,
¥D­n«ü¼Ð:
Primary Outcome Measures ƒÊ : 1.Percentage of participants with an IGA score of 0 or 1 and a reduction ≥2 points from Baseline to Week 16 [ Time Frame: Baseline to Week 16 ]




Evaluation of the Efficacy and Safety of Lebrikizumab (LY3650150) in Moderate to Severe Atopic Dermatitis (ADvocate2)
Study Type ƒÊ : Interventional (Clinical Trial)
Estimated Enrollment ƒÊ : 400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized, double-blind, parallel group, placebo controlled
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Double-blind
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo Controlled Trial to Evaluate the Efficacy and Safety of Lebrikizumab in Patients With Moderate to Severe Atopic Dermatitis.
Actual Study Start Date ƒÊ : November 8, 2019
Estimated Primary Completion Date ƒÊ : June 2021
Estimated Study Completion Date ƒÊ : December 2021

clinicaltrials.gov/ct2/show/NCT04178967?term=Lebrikizumab+PHASE+3&draw=2&rank=10



Primary Outcome Measures ƒÊ : 1.Percentage of participants with an IGA score of 0 or 1 and a reduction ≥2 points from Baseline to Week 16 [ Time Frame: Baseline to Week 16 ]



Secondary Outcome Measures ƒÊ : 1.Percentage of patients achieving EASI-75 (≥75% reduction in EASI score) from Baseline to Week 16 [ Time Frame: Baseline to Week 16 ]

2.Percentage of patients achieving EASI-90 (≥90% reduction in EASI score) from Baseline to Week 16 [ Time Frame: Baseline to Week 16 ]

3.Percentage change in Pruritus Numerical Rating Scale (NRS) score from Baseline to Week 16 [ Time Frame: Baseline to Week 16 ]

4.Percentage of patients with a Pruritus NRS score of ≥4-points at Baseline who achieve a ≥4-point reduction in Pruritus NRS score from Baseline to Week 16 [ Time Frame: Baseline to Week 16 ]

5.Percentage of patients with a Pruritus NRS score of ≥5-points at Baseline who achieve a ≥4-point reduction in Pruritus NRS score from Baseline to Week 16 [ Time Frame: Baseline to Week 16 ]

6.Percentage change in EASI score from Baseline to Week 16 [ Time Frame: Baseline to Week 16 ]

7.Change from Baseline to Week 16 in percent BSA [ Time Frame: Baseline to Week 16 ]

8.Percentage of patients achieving EASI-90 from Baseline to Week 4 [ Time Frame: Baseline to Week 4 ]

9.Percentage change in Sleep-loss score from Baseline to Week 16 [ Time Frame: Baseline to Week 16 ]

10.Change from Baseline in Sleep-loss score at Week 16 [ Time Frame: Baseline to Week 16 ]

11.Percentage of patients with a Pruritus NRS score of ≥4 points at Baseline who achieve a ≥4-point reduction from Baseline to Week 1 [ Time Frame: Baseline to Week 1 ]

12.Percentage of patients with a Pruritus NRS score of ≥4 points at Baseline who achieve a ≥4-point reduction from Baseline to Week 2 [ Time Frame: Baseline to Week 2 ]

13.Percentage of patients with a Pruritus NRS score of ≥4 points at Baseline who achieve a ≥4-point reduction from Baseline to Week 4 [ Time Frame: Baseline to Week 4 ]

14.Percentage of patients with a Pruritus NRS score of ≥5 points at Baseline who achieve a ≥4-point reduction from Baseline to Week 1 [ Time Frame: Baseline to Week 1 ]

15.Percentage of patients with a Pruritus NRS score of ≥5 points at Baseline who achieve a ≥4-point reduction from Baseline to Week 2 [ Time Frame: Baseline to Week 2 ]

16.Percentage of patients with a Pruritus NRS score of ≥5 points at Baseline who achieve a ≥4-point reduction from Baseline to Week 4 [ Time Frame: Baseline to Week 4 ]

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Dupilumab treatment in adults with moderate-to-severe atopic dermatitis


Lisa A Beck 1 , Diamant Thaçi, Jennifer D Hamilton, Neil M Graham, Thomas Bieber, Ross Rocklin, Jeffrey E Ming, Haobo Ren, Richard Kao, Eric Simpson, Marius Ardeleanu, Steven P Weinstein, Gianluca Pirozzi, Emma Guttman-Yassky, Mayte Suárez-Fariñas, Melissa D Hager, Neil Stahl, George D Yancopoulos, Allen R Radin

Affiliations Expand








PMID: 25006719
DOI: 10.1056/NEJMoa1314768










































Abstract


Background: Dupilumab, a fully human monoclonal antibody that blocks interleukin-4 and interleukin-13, has shown efficacy in patients with asthma and elevated eosinophil levels. The blockade by dupilumab of these key drivers of type 2 helper T-cell (Th2)-mediated inflammation could help in the treatment of related diseases, including atopic dermatitis.

Methods: We performed randomized, double-blind, placebo-controlled trials involving adults who had moderate-to-severe atopic dermatitis despite treatment with topical glucocorticoids and calcineurin inhibitors. Dupilumab was evaluated as monotherapy in two 4-week trials and in one 12-week trial and in combination with topical glucocorticoids in another 4-week study. End points included the Eczema Area and Severity Index (EASI) score, the investigator¡¦s global assessment score, pruritus, safety assessments, serum biomarker levels, and disease transcriptome.

Results: In the 4-week monotherapy studies, dupilumab resulted in rapid and dose-dependent improvements in clinical indexes, biomarker levels, and the transcriptome. The results of the 12-week study of dupilumab monotherapy reproduced and extended the 4-week findings: 85% of patients in the dupilumab group, as compared with 35% of those in the placebo group, had a 50% reduction in the EASI score (EASI-50, with higher scores in the EASI indicating greater severity of eczema) (P<0.001); 40% of patients in the dupilumab group, as compared with 7% in the placebo group, had a score of 0 to 1 (indicating clearing or near-clearing of skin lesions) on the investigator¡¦s global assessment (P<0.001); and pruritus scores decreased (indicating a reduction in itch) by 55.7% in the dupilumab group versus 15.1% in the placebo group (P<0.001). In the combination study, 100% of the patients in the dupilumab group, as compared with 50% of those who received topical glucocorticoids with placebo injection, met the criterion for EASI-50 (P=0.002), despite the fact that patients who received dupilumab plus glucocorticoids used less than half the amount of topical glucocorticoids used by those who received placebo plus the topical medication (P=0.16). Adverse events, such as skin infection, occurred more frequently with placebo; nasopharyngitis and headache were the most frequent adverse events with dupilumab.

Conclusions: Patients treated with dupilumab had marked and rapid improvement in all the evaluated measures of atopic dermatitis disease activity. Side-effect profiles were not dose-limiting. (Funded by Regeneron Pharmaceuticals and Sanofi; ClinicalTrials.gov numbers, NCT01259323, NCT01385657, NCT01639040, and NCT01548404.).

pubmed.ncbi.nlm.nih.gov/25006719/

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EASI-50 Dupilumab 71.4%/placebo(¹ï·Ó²Õ)18.8% .¡]1b ,n=21:16 )

Study Type ƒÊ : Interventional (Clinical Trial)
Actual Enrollment ƒÊ : 37 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Sequential Ascending, Repeated-Dose Study of the Safety, Tolerability, and Pharmacokinetics of Subcutaneous REGN668 in Patients With Moderate-to-Severe Atopic Dermatitis
Actual Study Start Date ƒÊ : July 31, 2011
Actual Primary Completion Date ƒÊ : March 31, 2012
Actual Study Completion Date ƒÊ : March 31, 2012


Experimental: Placebo
Placebo (for Dupilumab) as a single subcutaneous (SC) injection on Day 1, 8, 15, and 22
Drug: Placebo
A total of 4 doses were administered.

Other: Background treatment
Participants were required to apply stable doses of an additive-free, basic bland emollient on the affected areas of the skin twice daily throughout the study.


Experimental: Dupilumab 150 mg
Dupilumab 150 mg as a single SC injection on Day 1, 8, 15, and 22
Drug: Dupilumab
A total of 4 doses were administered.

Other Names:•REGN668
•SAR231893
•Dupixent

Other: Background treatment
Participants were required to apply stable doses of an additive-free, basic bland emollient on the affected areas of the skin twice daily throughout the study.


Experimental: Dupilumab 300 mg
Dupilumab 300 mg as a single SC injection on Day 1, 8, 15, and 22
Drug: Dupilumab
A total of 4 doses were administered.

Other Names:•REGN668
•SAR231893
•Dupixent

Other: Background treatment
Participants were required to apply stable doses of an additive-free, basic bland emollient on the affected areas of the skin twice daily throughout the study.

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All three trials assessed the primary endpoint, the change from baseline to Week 16 in the proportion of subjects with an IGA 0 (clear) or 1 (almost clear) and at least a 2-point improvement.

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Other endpoints included the proportion of subjects with EASI-75 (improvement of at least 75% in EASI score from baseline), and reduction in itch as defined by at least a 4point improvement in the peak pruritus NRS from baseline to Week 16.

www.accessdata.fda.gov/drugsatfda_docs/label/2017/761055lbl.pdf

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