Trial reportThorax2018
Novel anti-tumour necrosis factor receptor-1 (TNFR1) domain antibody prevents pulmonary inflammation in experimental acute lung injury.
Trial report in Thorax, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01587807 (A Two-part, Randomised, Placebo-controlled Study to Investigatethe Safety, Tolerability, Pharmacokinetics and Pharmacodynamicsof Single Doses of Inhaled GSK1995057 in Healthy Subjects), which is not on this map. Cited by 51 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Two-part, Randomised, Placebo-controlled Study to Investigatethe Safety, Tolerability, Pharmacokinetics and Pharmacodynamicsof Single Doses of Inhaled GSK1995057 in Healthy Subjects
Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 82 citations in OpenAlex.
- The genetic architecture of pneumonia susceptibility implicates mucin biology and a relationship with psychiatric illness.Nature communications · 2022Pooled it
- A nebulised antitumour necrosis factor receptor-1 domain antibody in patients at risk of postoperative lung injury: A randomised, placebo-controlled pilot study.European journal of anaesthesiology · 2020Trial
- Targeting PANoptosis: a promising therapeutic strategy for ALI/ARDS.Apoptosis : an international journal on programmed cell death · 2025Review
- Up-regulated vitronectin in Kawasaki disease shock syndrome serves as a potential biomarker.Translational pediatrics · 2025Article
- Advances in acute respiratory distress syndrome: focusing on heterogeneity, pathophysiology, and therapeutic strategies.Signal transduction and targeted therapy · 2025Review
- Effects ofBMJ open respiratory research · 2025Article
- Exploring TNFR1: from discovery to targeted therapy development.Journal of translational medicine · 2025Review
- Targeted delivery of flagellin by nebulization offers optimized respiratory immunity and defense against pneumococcal pneumonia.Antimicrobial agents and chemotherapy · 2024Article
- Principles and Therapeutics ofJournal of pharmacy & bioallied sciences · 2024Review
- IFN Receptor 2 Regulates TNF-α-Mediated Damaging Inflammation during Aspergillus Pulmonary Infection.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Single-Domain Antibodies-Novel Tools to Study and Treat Allergies.International journal of molecular sciences · 2024Review
- Single-domain antibodies as therapeutics for solid tumor treatment.Acta pharmaceutica Sinica. B · 2024Review
- The Role of Cytokines and Molecular Pathways in Lung Fibrosis Following SARS-CoV-2 Infection: A Physiopathologic (Re)view.Biomedicines · 2024Review
- Extensive acute and sustained changes to neutrophil proteomes post-SARS-CoV-2 infection.The European respiratory journal · 2024Observational
- TNF and TNF receptors as therapeutic targets for rheumatic diseases and beyond.Nature reviews. Rheumatology · 2023Review
- Evaluation of Plasma Biomarkers to Predict Major Adverse Kidney Events in Hospitalized Patients With COVID-19.American journal of kidney diseases : the official journal of the National Kidney Foundation · 2023Article
- Age-related changes in plasma biomarkers and their association with mortality in COVID-19.The European respiratory journal · 2023Article
- Apoptotic cell death in disease-Current understanding of the NCCD 2023.Cell death and differentiation · 2023Review
- Acute respiratory distress syndrome heterogeneity and the septic ARDS subgroup.Frontiers in immunology · 2023Review
- Multi-omic comparative analysis of COVID-19 and bacterial sepsis-induced ARDS.PLoS pathogens · 2022Article
Corrections and comments
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Authors and funding
19 authors at 7 institutions in 4 countries.
Funding
Abstract
backgroundTumour necrosis factor alpha (TNF-α) is a pleiotropic cytokine with both injurious and protective functions, which are thought to diverge at the level of its two cell surface receptors, TNFR1 and TNFR2. In the setting of acute injury, selective inhibition of TNFR1 is predicted to attenuate the cell death and inflammation associated with TNF-α, while sparing or potentiating the protective effects of TNFR2 signalling. We developed a potent and selective antagonist of TNFR1 (GSK1995057) using a novel domain antibody (dAb) therapeutic and assessed its efficacy in vitro, in vivo and in a clinical trial involving healthy human subjects.
methodsWe investigated the in vitro effects of GSK1995057 on human pulmonary microvascular endothelial cells (HMVEC-L) and then assessed the effects of pretreatment with nebulised GSK1995057 in a non-human primate model of acute lung injury. We then tested translation to humans by investigating the effects of a single nebulised dose of GSK1995057 in healthy humans (n=37) in a randomised controlled clinical trial in which subjects were subsequently exposed to inhaled endotoxin.
resultsSelective inhibition of TNFR1 signalling potently inhibited cytokine and neutrophil adhesion molecule expression in activated HMVEC-L monolayers in vitro (P<0.01 and P<0.001, respectively), and also significantly attenuated inflammation and signs of lung injury in non-human primates (P<0.01 in all cases). In a randomised, placebo-controlled trial of nebulised GSK1995057 in 37 healthy humans challenged with a low dose of inhaled endotoxin, treatment with GSK1995057 attenuated pulmonary neutrophilia, inflammatory cytokine release (P<0.01 in all cases) and signs of endothelial injury (P<0.05) in bronchoalveolar lavage and serum samples.
conclusionThese data support the potential for pulmonary delivery of a selective TNFR1 dAb as a novel therapeutic approach for the prevention of acute respiratory distress syndrome. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT01587807.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.