A phase Ib, randomised, double-blind, placebo-controlled, proof-of-concept study to evaluate the efficacy (anti-viral activity) and safety of SPX-001 in an influenza challenge model in healthy adult participants

开始日期2024-10-07

申办/合作机构-

100 项与 SPX-001 相关的临床结果

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100 项与 SPX-001 相关的转化医学

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100 项与 SPX-001 相关的专利（医药）

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项与 SPX-001 相关的文献（医药）

2019-08-01·Chemosphere2区 · 环境科学与生态学

Combined effects of okadaic acid and pectenotoxin-2, 13-desmethylspirolide C or yessotoxin in human intestinal Caco-2 cells

2区 · 环境科学与生态学

Article

作者: Alfonso Lampen ; Sabrina Barbé ; Valérie Fessard ; Albert Braeuning ; Ludovic Le Hégarat ; Stefanie Hessel-Pras ; Jimmy Alarcan ; Benjamin Kopp

Lipophilic phycotoxins are secondary metabolites produced by phytoplanktonic species. They accumulate in filtering shellfish and can cause human intoxications. Humans can be exposed to combinations of several phycotoxins. The toxicological effects of phycotoxin mixtures on human health are largely unknown. Published data on phycotoxin co-exposure show that okadaic acid (OA) is simultaneously found with pectenetoxin-2 (PTX-2), 13-desmethylspirolide C (also known as SPX-1), or yessotoxin (YTX). Therefore, the aim of this study was to examine the effects of three binary mixtures, OA/PTX-2, OA/SPX-1 and OA/YTX on human intestinal Caco-2 cells. A multi-parametric approach for cytotoxicity determination was applied using a high-content analysis platform, including markers for cell viability, oxidative stress, inflammation, and DNA damage. Mixtures effects were analyzed using two additivity mathematical models. Our assays revealed that OA induced cytotoxicity, DNA strand breaks and interleukin 8 release. PTX-2 slightly induced DNA strand breaks, whereas SPX-1 and YTX did not affect the investigated endpoints. The combination of OA with another toxin resulted in reduced toxicity at low concentrations, suggesting antagonistic effects, but in increased effects at higher concentrations, suggesting additive or synergistic effects. Taken together, our results demonstrated that the cytotoxic effects of binary mixtures of lipophilic phycotoxins could not be predicted by additivity mathematical models. In conclusion, the present data suggest that combined effects of phycotoxins may occur which might have the potential to impact on risk assessment of these compounds.

2018-02-01·Environmental Research2区 · 环境科学与生态学

Occurrence of cyclic imines in European commercial seafood and consumers risk assessment

2区 · 环境科学与生态学

Article

作者: Calis, Tanja ; de la Iglesia, Pablo ; Kotterman, Michiel ; Verbeke, Wim ; Diogene, Jorge ; Granby, Kit ; Samdal, Ingunn A ; Miles, Christopher O ; Tediosi, Alice ; Fernandez-Tejedor, Margarita ; Rambla-Alegre, Maria ; Barbosa, Vera ; Madorran, Eneko ; Sioen, Isabelle ; Sandvik, Morten ; Jacobs, Silke

Cyclic imines constitute a quite recently discovered group of marine biotoxins that act on neural receptors and that bioaccumulate in seafood. They are grouped together due to the imino group functioning as their common pharmacore, responsible for acute neurotoxicity in mice. Cyclic imines (CIs) have not been linked yet to human poisoning and are not regulated in the European Union (EU), although the European Food Safety Authority (EFSA) requires more data to perform conclusive risk assessment for consumers. Several commercial samples of bivalves including raw and processed samples from eight countries (Italy, Portugal, Slovenia, Spain, Ireland, Norway, The Netherlands and Denmark) were obtained over 2 years. Emerging cyclic imine concentrations in all the samples were analysed on a LC-3200QTRAP and LC-HRMS QExactive mass spectrometer. In shellfish, two CIs, pinnatoxin G (PnTX-G) and 13-desmethylspirolide C (SPX-1) were found at low concentrations (0.1-12µg/kg PnTX-G and 26-66µg/kg SPX-1), while gymnodimines and pteriatoxins were not detected in commercial (raw and processed) samples. In summary, SPX-1 (n: 47) and PnTX-G (n: 96) were detected in 9.4% and 4.2% of the samples, respectively, at concentrations higher than the limit of quantification (LOQ), and in 7.3% and 31.2% of the samples at concentrations lower than the LOQ (25µg/kg for SPX-1 and 3µg/kg for PnTX-G), respectively. For the detected cyclic imines, the average exposure and the 95th percentile were calculated. The results obtained indicate that it is unlikely that a potential health risk exists through the seafood diet for CIs in the EU. However, further information about CIs is necessary in order to perform a conclusive risk assessment.

Marine Drugs2区 · 医学

Confirmation of Pinnatoxins and Spirolides in Shellfish and Passive Samplers from Catalonia (Spain) by Liquid Chromatography Coupled with Triple Quadrupole and High-Resolution Hybrid Tandem Mass Spectrometry

2区 · 医学

ArticleOA

作者: García-Altares, María ; Bane, Vaishali ; Furey, Ambrose ; de la Iglesia, Pablo ; Diogène, Jorge ; Casanova, Alexis

Cyclic imines are lipophilic marine toxins that bioaccumulate in seafood. Their structure comprises a cyclic-imino moiety, responsible for acute neurotoxicity in mice. Cyclic imines have not been linked yet to human poisonings and are not regulated in Europe, although the European Food Safety Authority requires more data to perform a conclusive risk assessment for consumers. This work presents the first detection of pinnatoxin G (PnTX-G) in Spain and 13-desmethyl spirolide C (SPX-1) in shellfish from Catalonia (Spain, NW Mediterranean Sea). Cyclic imines were found at low concentrations (2 to 60 µg/kg) in 13 samples of mussels and oysters (22 samples analyzed). Pinnatoxin G has been also detected in 17 seawater samples (out of 34) using solid phase adsorption toxin tracking devices (0.3 to 0.9 µg/kg-resin). Pinnatoxin G and SPX-1 were confirmed with both low and high resolution (<2 ppm) mass spectrometry by comparison of the response with that from reference standards. For other analogs without reference standards, we applied a strategy combining low resolution MS with a triple quadrupole mass analyzer for a fast and reliable screening, and high resolution MS LTQ Orbitrap® for unambiguous confirmation. The advantages and limitations of using high resolution MS without reference standards were discussed.

项与 SPX-001 相关的新闻（医药）

2022-11-25

·Business Wire

SpectrumX Confirms Next Step in Clinical Development of Respiratory Drug Candidate SPX-001 After MHRA Meeting

LONDON--(BUSINESS WIRE)--SpectrumX, a UK-based healthcare and pharmaceutical company, today announces that following a constructive scientific advice meeting with the Medicines and Healthcare products Regulatory Agency (MHRA) on Monday, 14th November, the Company is prepared to move forward with the next stage in clinical development of its respiratory drug candidate SPX-001. Per regulatory guidelines, SpectrumX will submit a combined Clinical Trial and Ethics Committee application for a placebo-controlled phase Ib influenza viral challenge study of SPX-001 in healthy volunteers to the MHRA in December 2022. SPX-001 is SpectrumX’s nebulised respiratory infection drug candidate, based on the Company’s licensed hypochlorous acid (HOCl)-based SPC-069 drug substance, which is believed to have broad-spectrum antipathogenic properties. Commenting, Damien Hancox, CEO of SpectrumX said: “We believe SPX-001 could be a significant new weapon in the fight against viral respiratory infections, and this is a critical milestone in progressing our drug candidate toward targeted market authorisation approval. We would like to thank the MHRA for their helpful guidance and responses to our initial proposal to begin human clinical trials, and we hope this brings us another step closer to trialling what we believe is a revolutionary treatment for respiratory infections.” Dr Donna Lockhart, Consulting Head of Medicines at SpectrumX, said: “After productive discussions at a scientific advice meeting with the MHRA, during which we presented our lab-driven data, supporting evidence from existing literature, and key features of our novel solution, SPX-001, supporting its potential effects in combating respiratory infections, as well as our proposed clinical study protocol, I am pleased that we are one step closer to starting our clinical trial programme and the subsequent processes that are essential to market authorisation.” If approved, this will the first in-human trial to deliver SPX-001 via a nebulizer to test its efficacy and safety versus a placebo treatment in healthy subjects infected with influenza. Following successful completion of the planned trial, SpectrumX will move forward with further trials in patients with respiratory infections to gather the additional necessary data for a market authorisation approval. As previously announced, SpectrumX has already begun the production process for SPX-001, working with a GMP-certified partner, which will accelerate trial-readiness once requisite approvals have been received. - ENDS - For Investors SpectrumX is currently conducting a pre-IPO capital raise in advance of a planned listing on the London Stock Exchange. Interested prospective investors can learn more at https://spectrumx.com/investor-relations/. About SpectrumX SpectrumX is a UK-based healthcare and pharmaceuticals company focused on bringing to market an innovative respiratory infection therapy and the roll-out of the most powerful hand sanitiser in the world to the NHS and other healthcare clients. Both products utilise unique, patent-pending HOCl formulations. HOCl is naturally occurring in human white blood cells and is a key contributor in the immune response to infection. HOCl also has direct killing activity against bacteria, viruses and fungi. It is well-tolerated in humans while also being the most effective known disinfectant when used on surfaces. For more on SpectrumX, visit www.spectrumx.com.