Efficacy and Safety Study Exploring Nangibotide Treatment in COVID-19 pAtients With ventiLatory Support (ESSENTIAL) A Randomized, Double-blind, Placebo-controlled Study With Adaptive Features

This is a randomized, double-blind, placebo-controlled, in which one dose of nangibotide will be tested versus placebo.
All patients with a diagnosis of COVID-19, and a requirement for respiratory support will be considered for study participation. The applicable local requirements for informed consent will be followed. Where permissible, an emergency consent procedure will be followed for patients unable to provide consent by themselves. All potential study patients will receive standard of care treatment throughout the study. Patients will receive a continuous intravenous (i.v.) infusion of nangibotide at 1.0 mg/kg/h or a matching placebo. Treatment with study drug must be initiated as early as possible but no later than 48 hours after the initiation of ventilatory support (Patients will be treated for 5 days or until discharge from critical care, whichever is sooner). Follow-up visits will be performed on days 8 and 14. The end of study visit is at day 28. A further follow up visit will be undertaken on day 60.

开始日期2020-09-23

申办/合作机构

Inotrem SA

EUCTR2020-001504-42-BE

/ Not yet recruiting临床2/3期

Efficacy and Safety Study Exploring Nangibotide Treatment in COVID-19 pAtients with ventiLatory support (The ESSENTIAL Study). A randomized, double-blind, placebo-controlled study with adaptive features.

开始日期2020-06-12

申办/合作机构-

NCT04055909

/ Active, not recruiting临床2期

Efficacy, Safety and Tolerability of Nangibotide in Patients With Septic Shock. A Randomized, Double-blind, Placebo Controlled Dose Selection Study

This is a randomized, double-blind, placebo-controlled dose-selection study in which two doses of nangibotide are tested versus placebo.

开始日期2019-11-13

申办/合作机构

Inotrem SA

100 项与 Nangibotide 相关的临床结果

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100 项与 Nangibotide 相关的转化医学

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100 项与 Nangibotide 相关的专利（医药）

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项与 Nangibotide 相关的文献（医药）

2025-01-02·Burns & Trauma

Recent advances of precision immunotherapy in sepsis

Review

作者: Panagiotopoulos, Dimitrios ; Giamarellos-Bourboulis, Evangelos J ; Arapis, Antonios

Abstract:

Precision immunotherapy signifies the administration of the required type of immune intervention tailored to the state of immune activation at the appropriate time window. The classification of patients into the different states of immune activation is usually done by either a protein blood biomarker or a molecular blood endotype that is diagnostic of the precise immune state. Evidence coming from trials of the last decade suggests that immune interventions should be split into strategies aiming to attenuate the exaggerated immune responses, restore sepsis-induced immunoparalysis (SII) and restore the vascular tone. Suggested strategies to attenuate the immune responses are anakinra, nangibotide and tocilizumab. Biomarkers that guide their use are ferritin, soluble triggering receptor expressed on myeloid cells-1 and C-reactive protein. Suggested strategies to restore SII are nivolumab, recombinant human interferon-gamma, CYT107, granulocyte macrophage colony stimulating factor and IgM-enriched immunoglobulin prepapations. Biomarkers that guide their use are the expression of the human leukocyte antigen DR on blood monocytes, the absolute lymphocyte count and blood levels of immunoglobulin M. One recently suggested strategy to restore vascular tone is adrecizumab, the use of which is guided by blood levels of bio-adrenomedulin. The use of these precision treatment strategies is still hampered by the need for large-scale randomized controlled trials.

2024-09-01·Neurology-Neuroimmunology & Neuroinflammation

Single-Cell RNA Sequencing Reveals Transcriptional Landscape of Neutrophils and Highlights the Role of TREM-1 in EAE

Article

作者: Zhang, Huining ; Bi, Yanwei ; Han, Xianxian ; Yi, Le ; Ba, Yongbing ; Cui, Xiaoyang ; Li, Bin ; Quan, Moyuan

BACKGROUND AND OBJECTIVES:

Neutrophils, underestimated in multiple sclerosis (MS), are gaining increased attention for their significant functions in patients with MS and the experimental autoimmune encephalomyelitis (EAE) animal model. However, the precise role of neutrophils in cervical lymph nodes (CLNs), the primary CNS-draining lymph nodes where the autoimmune response is initiated during the progression of EAE, remains poorly understood.

METHODS:

Applying single-cell RNA sequencing (scRNA-seq), we constructed a comprehensive immune cell atlas of CLNs during development of EAE. Through this atlas, we concentrated on and uncovered the transcriptional landscape, phenotypic and functional heterogeneity of neutrophils, and their crosstalk with immune cells within CLNs in the neuroinflammatory processes in EAE.

RESULTS:

Notably, we observed a substantial increase in the neutrophil population in EAE mice, with a particular emphasis on the significant rise within the CLNs. Neutrophils in CLNs were categorized into 3 subtypes, and we explored the specific roles and developmental trajectories of each distinct neutrophil subtype. Neutrophils were found to engage in extensive interactions with other immune cells, playing crucial roles in T-cell activation. Moreover, our findings highlighted the strong migratory ability of neutrophils to CLNs, partly regulated by triggering the receptor expressed on myeloid cells 1 (TREM-1). Inhibiting TREM1 with LR12 prevents neutrophil migration both in vivo and in vitro. In addition, in patients with MS, we confirmed an increase in peripheral neutrophils with an upregulation of TREM-1.

DISCUSSION:

Our research provides a comprehensive and precise single-cell atlas of CLNs in EAE, highlighting the role of neutrophils in regulating the periphery immune response. In addition, TREM-1 emerged as an essential regulator of neutrophil migration to CLNs, holding promise as a potential therapeutic target in MS.

2024-02-01·Plant disease

Race and Virulence Dynamics of Puccinia triticina in China During 2007 to 2021

Article

作者: Liu, Bo ; Zhang, Hao ; Chen, Wanquan ; Li, Hongfu ; Gao, Li ; Liu, Taiguo ; Huang, Liang

The challenge of wheat leaf rust on wheat production is a recurring issue. Race identification of Puccinia triticina (Pt) serves as the foundation for preventing and controlling this disease. In a 15-year study, we identified 2,900 isolates of Pt from 20 provinces, cities, or autonomous regions in China during 2007 to 2021 and found 332 virulence phenotypes with 11 predominant phenotypes: PHT (8.3%), THT (5.4%), PHK (4.5%), PHJ (3.7%), THJ (3.6%), SHJ (3.5%), THS (3.3%), FGD (2.9%), THK (2.6%), PHS (2.4%), and PHD (2.0%). The virulence frequency for 40 Lr genes was identified across different years and areas; one major reason for the race dynamics was the attenuation to Lr1 and Lr26, which was more evident in southwest China. Lr9, Lr24, Lr28, Lr38, and Lr42 maintained effectiveness in China, while Lr2c, Lr10, Lr12, Lr14a, Lr14b, Lr22a, Lr33, and Lr36 nearly lost their effectiveness against wheat leaf rust disease. Twelve Lr sites were found to have differences in virulence frequencies with values greater than 20% across various locations; furthermore, the lowest and highest virulence values were observed in north China (Area 1) and northwest China (Area 5), respectively. According to phenotype dynamics, PHT, THT, FGD, THK, and PHS are more likely to persist over time. In addition, much attention should be given toward discovering rising combinations of virulent phenotypes.

项与 Nangibotide 相关的新闻（医药）

2024-02-27

·Business Wire

Sepsis Drug Pipeline Research Report 2024: Insights from 30 Companies and 35 Pipeline Drugs - ResearchAndMarkets.com

DUBLIN--( BUSINESS WIRE )--The "Sepsis - Pipeline Insight, 2024" clinical trials has been added to ResearchAndMarkets.com's offering. This report provides comprehensive insights about 30+ companies and 35+ pipeline drugs in Sepsis pipeline landscape. It covers the pipeline drug profiles, including clinical and nonclinical stage products. It also covers the therapeutics assessment by product type, stage, route of administration, and molecule type. It further highlights the inactive pipeline products in this space. The report outlays comprehensive insights of present scenario and growth prospects across the indication. A detailed picture of the Sepsis pipeline landscape is provided which includes the disease overview and Sepsis treatment guidelines. The assessment part of the report embraces, in depth Sepsis commercial assessment and clinical assessment of the pipeline products under development In the report, detailed description of the drug is given which includes mechanism of action of the drug, clinical studies, NDA approvals (if any), and product development activities comprising the technology, Sepsis collaborations, licensing, mergers and acquisition, funding, designations and other product related details. Report Highlights The companies and academics are working to assess challenges and seek opportunities that could influence Sepsis R&D. The therapies under development are focused on novel approaches to treat/improve Sepsis. Sepsis Emerging Drugs Chapters This segment of the Sepsis report encloses its detailed analysis of various drugs in different stages of clinical development, including phase II, I, preclinical and Discovery. It also helps to understand clinical trial details, expressive pharmacological action, agreements and collaborations, and the latest news and press releases. Sepsis Emerging Drugs Thymosin alpha 1: SciClone Pharmaceuticals Thymosin alpha 1, referred to as thymalfasin, is a synthetic 28-amino acid peptide with multiple biological activities primarily directed towards immune response enhancement. SciClone developed and launched Thymosin alpha 1, under the trade name Zadaxin, for the treatment of hepatitis B virus (HBV) infection and hepatitis C virus (HCV) infections. The drug is also being developed for the treatment of COVID 2019 infections. Scientific and clinical studies have shown that Thymosin alpha 1 helps to stimulate and direct the body's immune response to eradicate infectious diseases, such as HBV, HCV, bacterial, and fungal infections; to fight certain cancers such as melanoma and liver cancer; and to enhance response to vaccines. Clinical trials have shown that Thymosin alpha 1 improves survival in patients in intensive care units being treated for sepsis from severe bacterial infections. The therapy is being evaluated in Phase III stage to treat Sepsis. Currently, the drug is in Phase III stage of its development for the treatment of sepsis. Enibarcimab: AdrenoMed AG Enibarcimab (HAM8101; former name: Adrecizumab) a clinical-stage, first-in-class drug targeting loss of vascular integrity. The strong rationale for Enibarcimab is supported by the elegance of its mode of action, a monoclonal antibody that on binding to its target Adrenomedullin preserves its functionality as regulator of vascular integrity. Enibarcimab targets Adrenomedullin (ADM), a vasoprotective peptide hormone. ADM that remains in the bloodstream, however, has a different effect, one that helps mitigate sepsis: promoting stability of the endothelial barrier by restoring the cell junctions between endothelial cells that ordinarily regulate molecule transport and leakage. In health, levels of ADM in the bloodstream and extravascular space are in equilibrium so that endothelial barrier integrity is maintained and blood pressure remains normal. Currently, the drug is in Phase II stage of its development for the treatment of sepsis. M 6229: Matisse Pharmaceuticals Matisse's platform technology is based on the discovery that in many patients suffering from sepsis, proteins called histones are released by the innate immune system and dying cells into the blood stream, where they are toxic to other cells. Due to a self-enforcing cascade, people may die from organ failure within one or two days. Preclinical results have shown that by neutralizing the toxic histones with Matisse's product M6229, the negative cascade is terminated by neutralization of cationic histones by anionic M6229. Matisse claims to have identified an elegant solution for treating one of the major complications in sepsis by using a non-anticoagulant fraction of heparin called M6229 to neutralize toxic circulatory histones .Currently, the drug is in Phase I stage of its development for the treatment of sepsis. SNIPR 001: SNIPR Biome SNIPR001 is a novel, orally-administered antibiotic that is designed to precisely target difficult-to-treat bacterial infections. It is developed using SNIPR Biome's CRISPR-Guided VectorsT (CGVT Technology), which is designed to deliver CRISPR reagents into target bacterial cells. SNIPR001 is designed to target certain E. coli bacteria in the gut and thus prevent their translocation to the bloodstream, without affecting beneficial bacteria in the microbiome. It contains four CRISPR-armed phages that selectively target and eliminate E. coli strains that are resistant to fluoroquinolone, with demonstrated efficacy in animal disease models. Currently, the drug is in preclinical stage of its development for the treatment of sepsis. Sepsis: Pipeline Development Activities The report provides insights into different therapeutic candidates in phase II, I, preclinical and discovery stage. It also analyses Sepsis therapeutic drugs key players involved in developing key drugs. Pipeline Development Activities The report covers the detailed information of collaborations, acquisition and merger, licensing along with a thorough therapeutic assessment of emerging Sepsis drugs. Sepsis: Therapeutic Assessment Phases Late stage products (Phase III) Mid-stage products (Phase II) Early-stage product (Phase I) along with the details of Pre-clinical and Discovery stage candidates Discontinued & Inactive candidates Route of Administration Products have been categorized under various ROAs such as Oral Intravenous Subcutaneous Parenteral Topical Molecule Type Products have been categorized under various Molecule types such as Recombinant fusion proteins Small molecule Monoclonal antibody Peptide Polymer Gene therapy Product Type Sepsis Report Insights Sepsis Pipeline Analysis Therapeutic Assessment Unmet Needs Impact of Drugs Sepsis Report Assessment Pipeline Product Profiles Therapeutic Assessment Pipeline Assessment Inactive drugs assessment Unmet Needs Key Players SciClone Pharmaceuticals AdrenoMed AG Matisse Pharmaceuticals SNIPR Biome Tianjin Chase Sun Pharmaceutical Beijing Scitech-Mq Pharmaceuticals Recce Pharmaceuticals Inotrem Octapharma Shaperon Shionogi Pharmazz Seres Therapeutics Key Products Thymosin alpha 1 Enibarcimab M 6229 SNIPR 001 Kukoamine B ST-1830 RECCE 327 Nangibotide OctaplasLG HY209 Cefiderocol Centhaquine SER 155 For more information about this clinical trials report visit https://www.researchandmarkets.com/r/ixi7k5 About ResearchAndMarkets.com ResearchAndMarkets.com is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends.

临床2期临床3期临床1期

2024-01-08

·BioSpace

Inotrem Successfully Reaches Agreement with the FDA for a Phase 3 Registration Trial for Nangibotide in Septic Shock

Novel biomarker-guided Phase 3 registration trial in septic shock with an enrichment strategy-based patient selection. Historic paradigm shift in Primary endpoint: from all causes of mortality at Day 29 to proportion of patients alive and free of organ support at Day 29. PARIS--(BUSINESS WIRE)-- Inotrem, an advanced clinical stage biotech company specializing in immunotherapies for acute and chronic inflammatory syndromes, today announced the outcome of its regulatory interactions with the US Food and Drug Administration (FDA) to finalize the design of a single Phase 3 registration trial (ACCURATE) for nangibotide in septic shock. The ACCURATE trial design is built upon Phase 2 (ASTONISH) data that confirmed nangibotide’s strong efficacy and safety profile. The FDA accepts Inotrem’s innovative biomarker-driven precision medicine approach. The ACCURATE study will be centered on patients with high risk of mortality and morbidity as defined by a high concentration of the blood based sTREM-1 biomarker representing about 50 percent of the septic shock patients. This unique biomarker-guided approach allows for a single Phase 3 registration trial with a manageable number of subjects. The overall size of ACCURATE will be about 1,300 patients, with a primary analysis group of 900 patients. The primary endpoint of ACCURATE will be the proportion of patients alive and free of organ support at Day 29. ACCURATE will run globally and enroll patients in about 100 sites in the Americas, Europe and Japan. Inotrem is collaborating with Roche Diagnostics since 2017 to develop a sTREM-1 assay on the Elecsys/COBAS platform to identify patients that are both more at risk and more likely to benefit from nangibotide treatment. All sTREM-1 measurements in ACCURATE will be carried out on the Roche platform paving the way for the test to be available as a companion diagnostic at the time of nangibotide approval. “Inotrem is now in a leading position to conduct a single Phase 3 registration trial in a prospectively defined population of septic shock patients that are at high risk of morbidity and mortality. Our innovative, biomarker-guided strategy along with a new patient-related primary endpoint gives us the best possible chance of success in this challenging indication,” said Margarita Salcedo-Magguilli, Chief Development Officer of Inotrem. “The successful End of Phase 2 meeting with the FDA is a testament to the dedication and expertise of our team. We are energized by the support and guidance from the FDA which will enable us to accelerate the development of nangibotide and, ultimately, bring a potentially transformative treatment to septic shock patients in need of new alternatives," added Sven Zimmermann, Chief Executive Officer of Inotrem. Septic shock is the ultimate complication of sepsis and constitutes a high unmet medical need. The incidence of septic shock continuously raises and mortality remains elevated: it is the main cause of death in intensive care units. There is currently no specific therapy approved for this indication. Inotrem’s solution has the potential to become the first mechanism-based treatment for septic shock. With nangibotide, Inotrem has developed a novel approach of immunomodulation targeting the TREM-1 pathway to restore appropriate inflammatory response, vascular function and improve post septic shock survival. Based on its scientific leadership on TREM-1, next to acute inflammatory syndromes, the company has expanded its TREM-1 franchise into chronic inflammatory diseases. About Inotrem Inotrem S.A. is a biotechnology company specialized in immunotherapy for acute and chronic inflammatory syndromes. The company has developed a new concept of immunomodulation that targets the TREM-1 pathway to control unbalanced inflammatory responses. Through its proprietary technology platform, Inotrem has developed the first-in-class TREM-1 inhibitor, nangibotide, with potential applications in life-threatening immune dysregulations caused by severe infections such as septic shock and severe forms of COVID-19. In parallel, Inotrem has also launched an antibody-based program to develop a new therapeutic modality targeting chronic inflammatory diseases. The company was founded in 2013 by Dr Jean-Jacques Garaud, a former head of research and early development at the Roche Group, Prof. Sébastien Gibot and Dr Marc Derive. Inotrem is supported by leading European and North American investors. Inotrem is part of the French Tech 120, a government program dedicated to support the development of fast-growing startups. View source version on businesswire.com: Contacts Media contact for Inotrem Anne REIN Strategies & Image (S&I) anne.rein@strategiesimage.com +33 6 03 35 92 05 Source: Inotrem View this news release online at:

临床3期免疫疗法临床2期

2023-11-06

·BioSpace

Inotrem Receives Milestone Funding From the Crohn’s & Colitis Foundation IBD Ventures Program to Advance Its Inflammatory Bowel Disease Pipeline

Funding was provided on the basis of strong interim data successfully supporting the company’s innovative approach targeting the TREM-1 pathway to treat chronic inflammatory conditions. PARIS--(BUSINESS WIRE)-- Inotrem, an advanced clinical stage biotech company specialized in immunotherapies for acute and chronic inflammatory syndromes, announced today it received the second milestone-based funding from the American Crohn’s & Colitis Foundation’s IBD Ventures program. After initial support in December 2022, continuation of funding follows a thorough review of Inotrem’s interim data, successfully supporting the proof of concept of the company’s antibody program (INO-02). This program targets the TREM-1 pathway for Inflammatory Bowel Disease (IBD) and develops a biomarker-based personalized approach to identify the patients most likely to benefit from the treatment. The Crohn’s & Colitis Foundation, the leading nonprofit organization with the mission of curing Crohn’s disease and ulcerative colitis, decided to continue funding based on Inotrem’s successful achievement of the planned interim milestones. Launched in January 2023, the R&D project was designed to last over 12 months and will be a cornerstone in the preparation of Inotrem’s first-in-human clinical trial for INO-02. Inotrem’s antibody program targeting chronic inflammatory indications, such as IBD, is the company’s second asset next to nangibotide, dedicated to the treatment of acute inflammatory diseases (septic shock, Covid-19, myocardial infarction). Based on its cutting-edge proprietary technology platform and strong scientific leadership around the TREM-1 pathway, Inotrem has built a diversified drug portfolio targeting several inflammatory indications for which there are today no or limited specific treatment. “The continuous support of The Crohn’s & Colitis Foundation is a strong recognition of the potential of our therapeutic approach targeting the TREM-1 pathway and eloquently speaks to Inotrem’s ability to deploy its vision and strategy,” says Sven Zimmermann, CEO of Inotrem. “After our stringent evaluation, Inotrem has met predetermined research milestone expectations. We are looking forward to continuing this fruitful collaboration to advance our common quest for cures and the improvement of the quality of life of patients affected by inflammatory bowel diseases,” says Andrés Hurtado-Lorenzo PhD, SVP of Translational Research & IBD Ventures at The Crohn’s & Colitis Foundation. About Inotrem Inotrem S.A. is a biotechnology company specialized in immunotherapy for acute and chronic inflammatory syndromes. The company has developed a new concept of immunomodulation that targets the TREM-1 pathway to control unbalanced inflammatory responses. Through its proprietary technology platform, Inotrem has developed the first-in-class TREM-1 inhibitor, nangibotide, with potential applications in life-threatening immune dysregulations caused by severe infections such as septic shock and severe forms of COVID-19. In parallel, Inotrem has also launched an antibody-based program to develop a new therapeutic modality targeting chronic inflammatory diseases. The company was founded in 2013 by Dr Jean-Jacques Garaud, a former head of research and early development at the Roche Group, Prof. Sébastien Gibot and Dr Marc Derive. Inotrem is supported by leading European and North American investors Inotrem is part of the French Tech 120, a government program dedicated to support the development of fast-growing startups. About the American Crohn’s & Colitis Foundation’s IBD Ventures The Crohn's & Colitis Foundation is the leading non-profit organization focused on both research and patient support for inflammatory bowel disease (IBD), with the mission of curing Crohn's disease and ulcerative colitis, and of improving the quality of life of the millions of Americans living with IBD. The Foundation’s work is dramatically accelerating the research process through investment in research initiatives, while also providing extensive educational and support resources for patients and their families, medical professionals, and the public. IBD-Ventures is a dedicated funding mechanism to support product-oriented research and development programs. For more information, visit crohnscolitisfoundation.org, call 888-694-8872, or email info@crohnscolitisfoundation.org. View source version on businesswire.com: Contacts Media contact for Inotrem Anne REIN Strategies & Image (S&I) anne.rein@strategiesimage.com +33 6 03 35 92 05 Source: Inotrem View this news release online at:

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100 项与 Nangibotide 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
新型冠状病毒感染	临床2期	比利时	Inotrem SA	2020-09-23
新型冠状病毒感染	临床2期	法国	Inotrem SA	2020-09-23
脓毒性休克	临床2期	比利时	Inotrem SA	2017-07-03
脓毒性休克	临床2期	法国	Inotrem SA	2017-07-03
脓毒性休克	临床2期	荷兰	Inotrem SA	2017-07-03
脓毒性休克	临床2期	西班牙	Inotrem SA	2017-07-03
心肌梗塞	临床1期	法国	Inotrem SA	-

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04055909 (ASTONISH, Pubmed \| Lancet Respir Med)	临床2期	脓毒性休克	355	Nangibotide 0.3 mg/kg per h	壓窪餘壓醖壓蓋鬱構繭(鬱簾顧範遞選鏇艱鑰範) = 構遞衊繭醖齋膚鏇選糧齋網夢積鹽製鏇遞鏇艱 (範糧範構願鹹簾鹽糧憲 )	不佳	2023-10-01
				Nangibotide 1.0 mg/kg per h	壓窪餘壓醖壓蓋鬱構繭(鬱簾顧範遞選鏇艱鑰範) = 獵憲鑰遞觸選遞夢膚糧齋網夢積鹽製鏇遞鏇艱 (範糧範構願鹹簾鹽糧憲 )
NCT04429334 (ESSENTIAL, Pubmed)	临床2期	新型冠状病毒感染	220	Nangibotide	窪糧鏇壓簾選鑰積製齋(鬱壓鹽齋鹽願繭窪獵願): odds ratio = 1.79 (95% CI, 1.02 ~ 3.14), P-Value = 0.043	积极	2023-06-01
				Placebo
NCT04429334 (ESSENTIAL, Biospace) 人工标引	临床2期	新型冠状病毒感染	220	nangibotide	築衊醖衊網構選淵積窪(襯積獵獵鹽積鬱膚願鹽): P-Value = 0.040 更多	积极	2022-10-25
				Placebo
NCT04055909 (ASTONISH, PipelineReview) 人工标引	临床2期	脓毒性休克	-	Nangibotide	壓夢糧壓夢膚遞鑰蓋廠(簾窪糧繭廠夢製遞製鑰) = the benefit of nangibotide high dose treatment versus placebo was clinically and statistically significant at higher concentrations of sTREM-1, representing about 50% of the study population 淵願選齋壓築網鬱襯衊 (製範獵醖選窪憲網鹽衊 )	积极	2022-10-13
				Standard of Care
NCT03463044 (Pubmed \| Br J Clin Pharmacol)	临床1期	急性疾病	27	Nangibotide	遞廠遞憲繭顧選憲製壓(醖選餘願夢衊積鹹選築) = There were only few adverse events and they were mild in severity and considered unrelated to treatment 廠壓窪築網繭鬱網簾鹽 (襯願觸繭鹹糧顧壓網製 )	-	2018-10-01