Phase 2 Open Label Prospective Dose-Ranging Clinical Trial With Escalation and Expansion Cohorts to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Dosing, and Efficacy of RLS-0071 for the Treatment of Hospitalized Patients With Steroid-Refractory Acute Graft-versus-Host Disease

This study is a Open Label Prospective Dose-Ranging Escalation and Expansion Trial to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Dosing, and Efficacy of RLS-0071 for the secondary treatment of acute Graft-versus-Host Disease (aGvHD) in hospitalized patients who are steroid-refractory.

开始日期2024-08-01

申办/合作机构

ReAlta Life Sciences, Inc.初创企业

[+1]

NCT06175065 / Recruiting临床2期

A Phase 2a Randomized, Doubled-Blind, Placebo-Controlled Trial to Evaluate Safety, Pharmacokinetics and Pharmacokinetic-Pharmacodynamic Relationships of RLS-0071 in Patients With Acute Exacerbation of Chronic Obstructive Pulmonary Disease

AECOPD is a major cause of hospital admission and mortality. They contribute to long-term decline in lung function, physical capacity, and quality of life (QoL). RLS-0071 is a novel peptide being developed for the treatment of AECOPD. This study is designed to evaluate the safety and tolerability of RLS-0071 in the treatment of adults with moderate exacerbations of COPD.

开始日期2024-01-25

申办/合作机构

ReAlta Life Sciences, Inc.初创企业

NCT05778188 / Recruiting临床2期

A Phase 2, Two-Stage, Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of RLS-0071 in Newborns With Moderate or Severe Hypoxic-Ischemic Encephalopathy Undergoing Therapeutic Hypothermia With Long-Term Follow-Up

Hypoxic-ischemic encephalopathy (HIE) affects approximately 4,000 to 12,000 persons annually in the United States. Mortality from HIE has been reported up to 60%, with at least 25% of survivors left with significant neurocognitive disability. Despite this vital unmet medical need, no pharmacological adjunct or alternative therapy has proven beneficial in improving outcomes in neonatal HIE.
RLS-0071 is a novel peptide being developed for the treatment of neonatal HIE. This study is designed to evaluate the safety and tolerability of RLS-0071 in the treatment of newborns with moderate or severe HIE.

开始日期2023-07-27

申办/合作机构

ReAlta Life Sciences, Inc.初创企业

[+1]

100 项与 MPO x C1q 相关的临床结果

登录后查看更多信息

100 项与 MPO x C1q 相关的转化医学

登录后查看更多信息

0 项与 MPO x C1q 相关的专利（医药）

登录后查看更多信息

项与 MPO x C1q 相关的文献（医药）

2024-01-01·Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis

Systemic and local complement activation in peritoneal dialysis patients via conceivably distinct pathways

Article

作者: Berger, Stefan P ; Gaya da Costa, Mariana ; Poppelaars, Felix ; Pêgo, Catia ; Franssen, Casper FM ; Daha, Mohamed R ; Seelen, Marc A ; Pestana, Manuel ; van den Born, Jacob ; Faria, Bernardo ; Meter-Arkema, Anita H ; Lima, Carla

Background: Despite several advantages compared to haemodialysis (HD), peritoneal dialysis (PD) remains an underused dialysis technique due to its high technique failure rate related to membrane fibrosis and peritonitis events. Previous work has suggested a harmful role for the complement system in these processes, highlighting the need for a more comprehensive examination in PD. Methods: Plasma levels of C1q, mannose-binding lectin (MBL), Properdin, Factor D, C3d/C3-ratio and soluble membrane attack complex (sC5b-9) were determined in PD patients ( n = 55), HD patients ( n = 41), non-dialysis chronic kidney disease (CKD) patients ( n = 15) and healthy controls ( n = 14). Additionally, C1q, MBL, Properdin, Factor D and sC5b-9 levels were assessed in the peritoneal dialysis fluid (PDF). In a subgroup, interleukin-6, matrix metalloproteinase-2 (MMP-2), myeloperoxidase (MPO) and elastase were measured in the PDF. Results: PD patients had significantly higher systemic levels of sC5b-9 compared to healthy controls, CKD and HD patients ( p < 0.001). Plasma levels of C1q and C3d/C3-ratios were significantly associated with systemic sC5b-9 levels ( p < 0.001). Locally, sC5b-9 was detected in the PDF of all PD patients, and levels were approximately 33% of those in matched plasma, but they did not correlate. In the PDF, only Properdin levels remained significantly associated with PDF sC5b-9 levels in multivariate analysis ( p < 0.001). Additionally, PDF levels of sC5b-9 positively correlated with elastase, MPO and MMP-2 levels in the PDF ( p < 0.01). Conclusions: Our data reveal both systemic and local complement activation in PD patients. Furthermore, these two processes seem independent considering the involvement of different pathways and the lack of correlation.

2023-12-01·Journal of Muscle Research and Cell Motility

Bioinformatics analysis of paravertebral muscles atrophy in adult degenerative scoliosis

Article

作者: Rong, Zhigang ; Xu, Jianzhong ; Chen, Can ; Zhang, Chengmin ; Yang, Zhong ; Luo, Fei ; Pu, Rongxi

AbstractParavertebral muscles (PVM) act as one of the major dynamic factors to maintain human upright activities and play a remarkable role in maintaining the balance of the trunk. Adult degenerative scoliosis (ADS) has become one of the important causes of disability in the elderly population owing to the changes in spinal biomechanics, atrophy and degeneration of PVM, and imbalance of the spine. Previously, many studies focused on the physical evaluation of PVM degeneration. However, the molecular biological changes are still not completely known. In this study, we established a rat model of scoliosis and performed the proteomic analysis of the PVM of ADS. The results showed that the degree of atrophy, muscle fat deposition, and fibrosis of the PVM of rats positively correlated with the angle of scoliosis. The proteomic results showed that 177 differentially expressed proteins were present in the ADS group, which included 105 upregulated proteins and 72 downregulated proteins compared with the PVM in individuals without spinal deformities. Through the construction of a protein–protein interaction network, 18 core differentially expressed proteins were obtained, which included fibrinogen beta chain, apolipoprotein E, fibrinogen gamma chain, thrombospondin-1, integrin alpha-6, fibronectin-1, platelet factor 4, coagulation factor XIII A chain, ras-related protein Rap-1b, platelet endothelial cell adhesion molecule 1, complement C1q subcomponent subunit A, cathepsin G, myeloperoxidase, von Willebrand factor, integrin beta-1, integrin alpha-1, leukocyte surface antigen CD47, and complement C1q subcomponent subunit B. Further analysis of the Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) and immunofluorescence showed that the neutrophil extracellular traps (NETs) formation signaling pathway plays a major role in the pathogenesis of PVM degeneration in ADS. The results of the present study preliminarily laid the molecular biological foundation of PVM atrophy in ADS, which will provide a new therapeutic target for alleviating PVM atrophy and decreasing the occurrence of scoliosis.

2022-10-01·Indian Journal of Pathology and Microbiology

Role of light and immunofluorescence microscopy to differentiate primary and secondary membranous nephropathy

Article

作者: Basu, Keya ; Roychowdhury, Arpita ; Sengupta, Moumita ; Bandopadhyay, Manimoy ; Karmakar, Subhrajyoti ; Mukherjee, Sriranjan

Context:Membranous nephropathy (MN) causes nephrotic syndrome, mostly primary but may be associated with SLE, infections, cancer, or drug.Aims:To estimate clinical, serological, light microscopic, and direct immunofluorescence (DIF) findings to differentiate primary and secondary MN.Settings and Design:Prospective, cross-sectional, single-center study in a tertiary care hospital.Methods and Material:Total 51 cases from September 2019 to February 2020.Laboratory Data:Blood glucose, urine analysis, urea, creatinine, albumin, cholesterol, HBsAg, Anti HCV, ASO, ANA, MPO ANCA, PR3 ANCA, dsDNA, PLA2R, C3, and C4. Clinical parameters: age, sex, BP, skin lesions, arthralgia, edema, obesity. Renal biopsies examined with H and E, PAS, silver methanamine, MT stains. DIF done with IgG, IgM, IgA, C3c, C1q, kappa, and lambda.Statistical Analysis Used:Statistical software (Graph Pad PRISM 6) and Chi-square test).Results:Among 51 cases, 25 are primary and 26 are secondary MN with 22 being lupus nephritis, with 2 being post-infectious and the remaining 2 being proliferative glomerulonephritis with monoclonal immunoglobulin deposition (PGNMIDD) with kappa chain restriction. Mean age was 37 ± 12.18 and 30.69 ± 13.92 years for primary and secondary MN, respectively. Significant male preponderance in primary MN. Serum C4 significantly low in secondary MN (15.34 ± 9.59). Microscopic hematuria present in secondary MN. Mesangial and endocapillary hypercellularity are significant in secondary MN. IgG and kappa are significantly intense in primary whereas IgA, C3c, and C1q are significantly intense in secondary MN.Conclusions:Reliable differentiation between primary and secondary MN has important therapeutic implications.

项与 MPO x C1q 相关的新闻（医药）

2022-06-01

·BioSpace

ReAlta Life Sciences, Inc. Doses First Patient in Phase 1b Inhaled-LPS Challenge Clinical Trial to Support Development of RLS-0071 in Severe Asthma

June 1, 2022 12:35 UTC NORFOLK, Va.--(BUSINESS WIRE)-- ReAlta Life Sciences, Inc. (“ReAlta”) a clinical stage, rare disease company addressing life-threatening diseases through harnessing the power of the immune system, today announced the dosing of the first patient in its Phase 1b Inhaled- lipopolysaccharide (LPS) challenge clinical trial in healthy volunteers to support development of RLS-0071 in severe asthma. RLS-0071 is the Company’s lead dual-action complement inhibitor and innate anti-inflammatory peptide in development as a treatment for hypoxic ischemic encephalopathy, severe asthma, and other rare diseases. “RLS-0071’s dual anti-inflammatory mechanism of action has potential utility across many inflammatory conditions,” said Kenji Cunnion, M.D., M.P.H., Chief Medical Officer of ReAlta. “We have already shown that RLS-0071 was well tolerated and demonstrated target engagement in a Phase 1 clinical trial in healthy volunteers. This study will inform development plans for RLS-0071 in severe asthma and related pulmonary programs, as well as other programs in neurology, including hypoxic-ischemic encephalopathy. We look forward to the readout of the trial.” The clinical trial is a Phase 1b, randomized, double-blind, placebo-controlled, proof of mechanism, and dose range finding study to assess the safety, tolerability and pharmacodynamics including change in count of sputum neutrophils and neutrophil effectors of RLS-0071 in 48 healthy adult subjects after challenge with inhaled LPS. When inhaled, LPS temporarily induces neutrophilic lung disease, creating a similar phenotype and mechanism to severe asthma. The trial is being run in collaboration with the Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), in Hannover, Germany. More information about the trial can be found at clinicaltrials.gov (NCT # 05351671). About ReAlta ReAlta Life Sciences, Inc. is a clinical-stage, rare disease biotech company dedicated to harnessing the power of the immune system to address life threatening diseases. The Company’s EPICC peptides are based on research into the human astrovirus HAstV-1, which causes a non-inflammatory, self-limiting gastroenteritis unique among viruses by inhibiting components of the innate immune system. ReAlta’s therapeutic peptides leverage these virus-derived mechanisms to rebalance complement and inflammatory processes in the body. The company’s pipeline is led by RLS-0071, which has received IND clearance, and Orphan Drug Designation by the U.S. Food and Drug Administration and European Medicines Agency for the treatment of hypoxic-ischemic encephalopathy (HIE) in neonates. RLS-0071 is a 15 amino acid peptide that both inhibits humoral inflammation by blocking classical pathway complement activation and cellular inflammation by blocking the neutrophil effectors myeloperoxidase (MPO) and neutrophil extracellular traps (NETs). The company launched in 2018 and is located in Norfolk, Virginia. For more information, please visit .

合作孤儿药